DT-Web

DB00631 - Clofarabine


Identification
Name Clofarabine
Accession Number DB00631 (APRD00878, DB07554)
Type small molecule
Description Clofarabine is a purine nucleoside antimetabolite that is being studied in the treatment of cancer. It is marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. Clofarabine is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if the drug extends life expectancy. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 303.677
Groups approved
Monoisotopic Weight 303.053445155
Pharmacology
Indication For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use.
Mechanism of action Clofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death.
Absorption Not Available
Protein binding 47% bound to plasma proteins, predominantly to albumin.
Biotransformation Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phosphokinases to the active 5’-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine.
Route of elimination Based on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine unchanged.
Toxicity There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m2 basis) has been 70 mg/m2/day × 5 days (2 pediatric ALL patients). The toxicities included in these 2 patients included grade 4 hyperbilirubinemia, grade 2 and 3 vomiting, and grade 3 maculopapular rash.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Leflunomide Immunosuppressants such as clofarabine may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
Natalizumab Immunosuppressants such as clofarabine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
Pimecrolimus Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as clofarabine. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Roflumilast Roflumilast may enhance the immunosuppressive effect of Immunosuppressants. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
Tacrolimus Tacrolimus (topical) may enhance the adverse/toxic effect of immunosuppressants such as clofarabine. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions
  • Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

Targets


DNA polymerase alpha catalytic subunit
Name DNA polymerase alpha catalytic subunit
Gene Name POLA1
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. - Pubmed
  • Clofarabine. Drugs R D. 2004;5(4):213-7. - Pubmed
  • Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. - Pubmed
  • Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. - Pubmed
  • Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. - Pubmed
  • Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. - Pubmed
  • Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. Epub 2009 Jul 1. - Pubmed
DTHybrid score 0.6323
Ribonucleoside-diphosphate reductase large subunit
Name Ribonucleoside-diphosphate reductase large subunit
Gene Name RRM1
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. - Pubmed
  • Clofarabine. Drugs R D. 2004;5(4):213-7. - Pubmed
  • Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. - Pubmed
  • Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. - Pubmed
  • Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. - Pubmed
  • Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. - Pubmed
  • Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. Epub 2009 Jul 1. - Pubmed
DTHybrid score 0.6398
DNA
Name DNA
Gene Name Not Available
Pharmacological action yes
Actions other/unknown
References
  • Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. - Pubmed
  • Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. - Pubmed
DTHybrid score Not Available

Enzymes


Deoxycytidine kinase
Name Deoxycytidine kinase
Gene Name DCK
Actions substrate
References
  • Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. - Pubmed
  • Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. Epub 2009 Jul 1. - Pubmed
  • Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. - Pubmed
DTHybrid score 0.8094

Transporters


ATP-binding cassette sub-family G member 2
Name ATP-binding cassette sub-family G member 2
Gene Name ABCG2
Actions substrate
References
  • de Wolf C, Jansen R, Yamaguchi H, de Haas M, van de Wetering K, Wijnholds J, Beijnen J, Borst P: Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther. 2008 Sep;7(9):3092-102. Epub 2008 Sep 2. - Pubmed
DTHybrid score 0.262

Predictions


Id Partner name Gene Name Score
6171 Solute carrier family 28 member 3 SLC28A3 0.2281
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.1914
6083 Deoxyguanosine kinase, mitochondrial DGUOK 0.1744
3690 Class B acid phosphatase precursor aphA 0.0952
6112 DNA polymerase epsilon subunit 3 POLE3 0.082
6111 DNA polymerase epsilon subunit 4 POLE4 0.082
6108 Ribonucleoside-diphosphate reductase subunit M2 B RRM2B 0.082
6110 DNA polymerase epsilon subunit 2 POLE2 0.0819
6109 DNA polymerase epsilon catalytic subunit A POLE 0.0819
3957 Adenosine deaminase ADA 0.0786
1588 Multidrug resistance protein 1 ABCB1 0.0778
4119 Cytochrome P450 2D6 CYP2D6 0.0666
1064 DNA (cytosine-5)-methyltransferase 1 DNMT1 0.0636
4218 Ribonucleoside-diphosphate reductase M2 subunit RRM2 0.06
3611 Cytidine deaminase cdd 0.057
3707 Cytidine deaminase cdd 0.057
4211 Cytidine deaminase CDA 0.057
702 UMP-CMP kinase CMPK1 0.0504
6148 Multidrug resistance-associated protein 7 ABCC10 0.0483
4512 Cytochrome P450 3A4 CYP3A4 0.047
24 Thymidylate synthase TMP1 0.0454
359 Thymidylate synthase TYMS 0.0454
2626 Thymidylate synthase thyA 0.0454
2729 Thymidylate synthase thyA 0.0454
5352 Thymidylate synthase THYA 0.0454
6144 Solute carrier family 22 member 2 SLC22A2 0.0436
6145 Solute carrier family 22 member 1 SLC22A1 0.0429
277 Purine nucleoside phosphorylase PNP 0.0376
2870 Purine nucleoside phosphorylase punA 0.0376
2945 Purine nucleoside phosphorylase punA 0.0376
4659 Purine nucleoside phosphorylase TM_1596 0.0376
4825 Purine nucleoside phosphorylase TTHA1435 0.0376
4757 Cytochrome P450 2C9 CYP2C9 0.0319
862 Multidrug resistance-associated protein 1 ABCC1 0.0311
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0295
4118 Cytochrome P450 3A5 CYP3A5 0.0287
4200 Cytochrome P450 1A2 CYP1A2 0.0255
6016 Cytochrome P450 2C19 CYP2C19 0.0243
4924 Cytochrome P450 2C8 CYP2C8 0.0236
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0217
1043 Trifunctional purine biosynthetic protein adenosine-3 [Includes: Phosphoribosylamine--glycine ligase GART 0.0205
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.0183
1729 Solute carrier family 22 member 6 SLC22A6 0.018
6107 Cytochrome P450 3A7 CYP3A7 0.0177
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0173
1830 5'-nucleotidase NT5E 0.0163
125 DNA polymerase beta POLB 0.0153
6024 Cytochrome P450 1A1 CYP1A1 0.0152
587 Serum albumin ALB 0.0142
1898 Cytochrome P450 1B1 CYP1B1 0.014
365 Dihydrofolate reductase DHFR 0.0136
2381 Dihydrofolate reductase DFR1 0.0136
2833 Dihydrofolate reductase Not Available 0.0136
2931 Dihydrofolate reductase folA 0.0136
3544 Dihydrofolate reductase folA 0.0136
3682 Dihydrofolate reductase folA 0.0136
6642 Dihydrofolate reductase folA 0.0136
6756 Dihydrofolate reductase dfrA 0.0136
1353 DNA topoisomerase 1 TOP1 0.0135
3552 DNA topoisomerase 1 topA 0.0135
844 Epidermal growth factor receptor EGFR 0.0134
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0134
2164 Multidrug resistance-associated protein 4 ABCC4 0.0128
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0124
6143 Solute carrier family 22 member 7 SLC22A7 0.0122
424 Dihydroorotate dehydrogenase, mitochondrial DHODH 0.0122
776 Bile salt export pump ABCB11 0.0121
342 P protein [Includes: DNA-directed DNA polymerase P 0.0116
612 P protein [Includes: DNA-directed DNA polymerase P 0.0116
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0114
6030 Cytochrome P450 2B6 CYP2B6 0.0113
6147 Solute carrier family 22 member 3 SLC22A3 0.011
504 Mast/stem cell growth factor receptor KIT 0.0107
6031 Cytochrome P450 3A43 CYP3A43 0.0106
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0105
677 Choline-phosphate cytidylyltransferase A PCYT1A 0.0105
6137 Multidrug resistance-associated protein 6 ABCC6 0.0103
147 Aldehyde dehydrogenase, mitochondrial ALDH2 0.0103
5626 Nucleoside diphosphate kinase B NME2 0.0094
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0093
117 Sterol O-acyltransferase 1 SOAT1 0.009
385 Potassium-transporting ATPase alpha chain 1 ATP4A 0.009
817 DNA topoisomerase 2-alpha TOP2A 0.0088
6013 Cytochrome P450 2E1 CYP2E1 0.0085
33 Cystine/glutamate transporter SLC7A11 0.0084
5294 Nucleoside diphosphate kinase A NME1 0.0083
567 Receptor tyrosine-protein kinase erbB-2 ERBB2 0.0076
6142 Solute carrier family 22 member 8 SLC22A8 0.0073
259 Microsomal triglyceride transfer protein large subunit MTTP 0.0072
6599 HTH-type transcriptional regulator ttgR ttgR 0.0071
698 B-Raf proto-oncogene serine/threonine-protein kinase BRAF 0.007
228 Beta platelet-derived growth factor receptor PDGFRB 0.007
102 DNA topoisomerase I, mitochondrial TOP1MT 0.007
992 Protein tyrosine kinase 2 beta PTK2B 0.0067
950 Alpha platelet-derived growth factor receptor PDGFRA 0.0063
176 30S ribosomal protein S10 rpsJ 0.006
6175 30S ribosomal protein S10 rpsJ 0.006
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.006
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.006
4117 Probable pyruvate-flavodoxin oxidoreductase ydbK 0.006
4120 NADPH--cytochrome P450 reductase POR 0.0058
1024 Solute carrier family 22 member 11 SLC22A11 0.0058
5718 Cytochrome P450 2A6 CYP2A6 0.0057
17 Proto-oncogene tyrosine-protein kinase ABL1 ABL1 0.0057
685 Oxygen-insensitive NADPH nitroreductase nfsA 0.0057
6945 Oxygen-insensitive NADPH nitroreductase rdxA 0.0057
26 Vascular endothelial growth factor receptor 3 FLT4 0.0053
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0053
887 DNA gyrase subunit B gyrB 0.0051
4150 DNA gyrase subunit B gyrB 0.0051
6225 DNA gyrase subunit B gyrB 0.0051
32 Vascular endothelial growth factor receptor 1 FLT1 0.0051
407 Vascular endothelial growth factor receptor 2 KDR 0.0051
136 Estrogen receptor ESR1 0.005
1650 Heme carrier protein 1 SLC46A1 0.005
5787 Angiopoietin-1 receptor TEK 0.0049
20 Prostaglandin G/H synthase 1 PTGS1 0.0049
908 Glutathione S-transferase theta-1 GSTT1 0.0049
29 Tubulin beta-1 chain TUBB1 0.0049
40 RAF proto-oncogene serine/threonine-protein kinase RAF1 0.0048
2539 Tubulin alpha-1 chain TUBA4A 0.0045
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0043
468 Cytochrome P450 4A11 CYP4A11 0.0043
6141 Sodium/bile acid cotransporter SLC10A1 0.0043
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0043
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0042
869 Estrogen receptor beta ESR2 0.0042
6163 Copper-transporting ATPase 2 ATP7B 0.0041
6165 Copper-transporting ATPase 1 ATP7A 0.0041
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0041
904 Glutathione S-transferase P GSTP1 0.004
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.004
165 FL cytokine receptor FLT3 0.004
6146 High affinity copper uptake protein 1 SLC31A1 0.004
6220 Aryl hydrocarbon receptor AHR 0.0039
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0039
4152 Superoxide dismutase [Cu-Zn] SOD1 0.0039
6106 Cytochrome P450 2C18 CYP2C18 0.0038
3811 Cytochrome P450 19A1 CYP19A1 0.0037
3947 Xanthine dehydrogenase/oxidase XDH 0.0037
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0036
731 HIV-1 protease HIV-1 protease 0.0036
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0035
896 Glutathione S-transferase Mu 1 GSTM1 0.0035
3917 Methylenetetrahydrofolate reductase MTHFR 0.0034
3856 Fibroblast growth factor receptor 3 FGFR3 0.0033
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0033
4177 Proto-oncogene tyrosine-protein kinase receptor ret RET 0.0032
70 Type-1 angiotensin II receptor AGTR1 0.0032
461 Glycine receptor subunit alpha-3 GLRA3 0.0032
118 Organic cation/carnitine transporter 2 SLC22A5 0.0031
293 Gamma-glutamyl hydrolase GGH 0.0031
1757 Myeloperoxidase MPO 0.0031
6161 Probable low affinity copper uptake protein 2 SLC31A2 0.0031
3854 Basic fibroblast growth factor receptor 1 FGFR1 0.003
738 Monocarboxylate transporter 1 SLC16A1 0.003
756 Sex hormone-binding globulin SHBG 0.003
5923 Microtubule-associated protein tau MAPT 0.003
5924 Microtubule-associated protein 4 MAP4 0.003
469 Annexin A1 ANXA1 0.003
3950 Cell division protein kinase 9 CDK9 0.0029
3968 Cell division protein kinase 8 CDK8 0.0029
78 Acetyl-CoA acetyltransferase, mitochondrial ACAT1 0.0028
1852 Microtubule-associated protein 2 MAP2 0.0028
4604 Liver carboxylesterase 1 CES1 0.0027
6136 Multidrug resistance-associated protein 5 ABCC5 0.0027
106 Cannabinoid receptor 2 CNR2 0.0027
951 Macrophage colony-stimulating factor 1 receptor CSF1R 0.0027
373 Transthyretin TTR 0.0027
273 Apoptosis regulator Bcl-2 BCL2 0.0026
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0026
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0026
68 Cannabinoid receptor 1 CNR1 0.0026
4192 DNA topoisomerase 2-beta TOP2B 0.0026
890 Niemann-Pick C1-like protein 1 NPC1L1 0.0026
804 Mitochondrial folate transporter/carrier SLC25A32 0.0026
718 Folate receptor gamma FOLR3 0.0026
299 Folate receptor beta FOLR2 0.0026
290 Prostaglandin G/H synthase 2 PTGS2 0.0026
936 Ephrin type-A receptor 2 EPHA2 0.0026
3959 Cell division protein kinase 4 CDK4 0.0025
511 5-hydroxytryptamine 1F receptor HTR1F 0.0025
3482 Cell division protein kinase 7 CDK7 0.0025
183 Vascular endothelial growth factor A VEGFA 0.0024
1760 Aminopeptidase N ANPEP 0.0024
6843 Aminopeptidase N pepN 0.0024
3941 Amine oxidase [flavin-containing] A MAOA 0.0023
3955 Cell division protein kinase 6 CDK6 0.0023
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.0023
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0022
823 Fibroblast growth factor receptor 2 FGFR2 0.0022
778 Cysteinyl leukotriene receptor 1 CYSLTR1 0.0022
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0022
6182 Cytochrome P450 2J2 CYP2J2 0.0022
3810 Catechol O-methyltransferase COMT 0.0022
937 Proto-oncogene tyrosine-protein kinase LCK LCK 0.0021
1618 High affinity nerve growth factor receptor NTRK1 0.0021
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0021
5287 Signaling protein Not Available 0.0021
2038 Inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB 0.0021
5288 Shikimate kinase aroK 0.0021
5304 UPF0166 protein TM_0021 TM_0021 0.0021
5270 ATP-dependent Clp protease ATP-binding subunit clpX clpX 0.0021
5314 UPF0079 ATP-binding protein HI0065 HI_0065 0.0021
5259 Transcriptional regulator ntrC1 0.0021
6699 Transcriptional regulator Cgl2612 0.0021
5290 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0021
5638 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0021
3199 Phosphopantetheine adenylyltransferase coaD 0.0021
3543 Phosphopantetheine adenylyltransferase coaD 0.0021
3567 Phosphopantetheine adenylyltransferase coaD 0.0021
5289 Phosphopantetheine adenylyltransferase coaD 0.0021
2874 Nitrogenase iron protein 1 nifH1 0.0021
4346 Polynucleotide kinase pseT 0.0021
5293 Shikimate kinase 2 aroL 0.0021
5292 Putative partitioning protein TT_C1605 0.0021
5281 Plasmid segregation protein parM parM 0.0021
5305 Phosphoribosylaminoimidazole carboxylase ATPase subunit purK 0.0021
5299 D-alanine--D-alanine ligase ddl 0.0021
6598 D-alanine--D-alanine ligase ddl 0.0021
5276 Chromosomal replication initiator protein dnaA dnaA 0.0021
5266 Activator of hgdC 0.0021
4794 Phosphoenolpyruvate carboxykinase [ATP] pckA 0.0021
5283 D-alanine--D-alanine ligase B ddlB 0.0021
5275 Multidrug resistance ABC transporter ATP-binding and permease protein lmrA 0.0021
5308 Preprotein translocase secA 1 subunit secA1 0.0021
5315 Chaperone protein htpG htpG 0.0021
1549 Heat shock 70 kDa protein 1 HSPA1A 0.0021
5284 Large T antigen Not Available 0.0021
3777 ATP-dependent Clp protease ATP-binding subunit clpA clpA 0.0021
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0021
5261 Phosphoribosylformylglycinamidine synthase purL 0.0021
5277 Preprotein translocase subunit secA secA 0.0021
5291 Glycogen synthase 1 glgA1 0.0021
5264 DNA replication protein REP 0.0021
5285 Kinesin heavy chain KIF5B 0.0021
1742 D-HSCDK2 CDK2deltaT 0.002
1771 Cell division control protein 2 homolog CDK1 0.002
3321 Cell division control protein 2 homolog CRK2 0.002
1058 Cell division protein kinase 5 CDK5 0.002
6166 Organic solute transporter subunit alpha OSTA 0.0019
6167 Organic solute transporter subunit beta OSTB 0.0019
824 Sodium-dependent serotonin transporter SLC6A4 0.0019
6837 Serine/threonine-protein kinase 17B STK17B 0.0018
6836 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial HIBCH 0.0018
725 5-hydroxytryptamine 1D receptor HTR1D 0.0018
885 5-hydroxytryptamine 1B receptor HTR1B 0.0018
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0018
2450 Tyrosine-protein kinase ITK/TSK ITK 0.0018
871 Glucocorticoid receptor NR3C1 0.0018
3809 Estrogen-related receptor gamma ESRRG 0.0018
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0018
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0017
275 Arachidonate 5-lipoxygenase ALOX5 0.0017
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0017
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0017
2216 Fibroblast growth factor receptor 4 FGFR4 0.0017
6228 Nuclear receptor coactivator 1 NCOA1 0.0017
4217 Telomerase reverse transcriptase TERT 0.0017
1063 Signal transducer and activator of transcription 5B STAT5B 0.0017
935 Proto-oncogene tyrosine-protein kinase Yes YES1 0.0017
6241 Nuclear receptor coactivator 2 NCOA2 0.0017
239 Coagulation factor X F10 0.0017
4226 Uridine phosphorylase 2 UPP2 0.0017
933 Proto-oncogene tyrosine-protein kinase Src SRC 0.0017
161 Tubulin beta chain TUBB 0.0016
312 Tubulin beta chain TUB2 0.0016
4106 Guanylate kinase GUK1 0.0016
4516 Guanylate kinase gmk 0.0016
320 5-hydroxytryptamine 1A receptor HTR1A 0.0016
6277 Heat shock cognate 71 kDa protein HSPA8 0.0016
3390 Aminoglycoside 3'-phosphotransferase aphA 0.0016
6029 Aminoglycoside 3'-phosphotransferase aphA1 0.0016
4837 Cag-alfa cag-alfa 0.0016
5646 Galactokinase GALK1 0.0016
5302 TrwB trwB 0.0016
4839 DNA polymerase III subunit tau dnaX 0.0016
4774 NTPase P4 Not Available 0.0016
4838 PMS1 protein homolog 2 PMS2 0.0016
5265 FtsH ftsH 0.0016
6656 UDP-glucuronosyltransferase 3A1 UGT3A1 0.0016
340 Apoptotic protease-activating factor 1 APAF1 0.0016
4225 Uridine phosphorylase 1 UPP1 0.0016
2270 Dephospho-CoA kinase coaE 0.0016
5189 Trimethylamine dehydrogenase tmd 0.0016
713 Sodium-dependent dopamine transporter SLC6A3 0.0016
2284 Adenylate kinase adk 0.0016
2296 Adenylate kinase adk 0.0016
2311 Adenylate kinase adk 0.0016
2312 Adenylate kinase Not Available 0.0016
934 Proto-oncogene tyrosine-protein kinase Fyn FYN 0.0015
5295 2-keto-3-deoxy-gluconate kinase TT_P0036 0.0015
2751 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0015
4755 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0015
3470 Hypothetical protein MG245 homolog MPN_348 0.0015
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0015
3175 Glutamate--cysteine ligase gshA 0.0015
3426 Glutamine synthetase glnA 0.0015
3987 Glutamine synthetase GLUL 0.0015
5300 Antigen peptide transporter 1 TAP1 0.0015
2683 Mono-ADP-ribosyltransferase C3 C3 0.0015
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0015
2390 Nonsecretory ribonuclease RNASE2 0.0014
413 Amidophosphoribosyltransferase PPAT 0.0014
2515 Amidophosphoribosyltransferase purF 0.0014
3714 Amidophosphoribosyltransferase purF 0.0014
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0014
5312 Kinesin-like protein KIF1A KIF1A 0.0014
484 Tyrosine-protein kinase ABL2 ABL2 0.0014
3923 Cholinesterase BCHE 0.0014
2282 Protein recA recA 0.0014
2315 Protein recA recA 0.0014
2332 Protein recA recA 0.0014
5263 Protein recA recA 0.0014
2599 Tyrosine-protein kinase HCK HCK 0.0014
5798 Mitogen-activated protein kinase 11 MAPK11 0.0014
2922 Glycerol kinase glpK 0.0014
408 Riboflavin kinase RFK 0.0014
2320 Thymidine kinase, cytosolic TK1 0.0014
796 Inosine-5'-monophosphate dehydrogenase 2 IMPDH2 0.0013
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0013
838 Inosine-5'-monophosphate dehydrogenase 1 IMPDH1 0.0013
6824 Tyrosine-protein kinase Lyn LYN 0.0013
421 Calcium signal-modulating cyclophilin ligand CAMLG 0.0013
3868 Calcineurin subunit B isoform 2 PPP3R2 0.0013
5271 Focal adhesion kinase 1 PTK2 0.0013
6344 ATP synthase subunit gamma, mitochondrial ATP5C1 0.0013
6343 ATP synthase subunit beta, mitochondrial ATP5B 0.0013
6342 ATP synthase subunit alpha, mitochondrial ATP5A1 0.0013
1152 Glycogen phosphorylase, muscle form PYGM 0.0013
2615 Chemotaxis protein cheA cheA 0.0013
5278 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 PAPSS1 0.0013
1864 RET proto-oncogene RET 0.0013
6170 ATP-binding cassette sub-family A member 3 ABCA3 0.0013
1950 Epithelial discoidin domain-containing receptor 1 DDR1 0.0013
6094 BCR/ABL fusion protein isoform X9 BCR/ABL fusion 0.0013
6832 Serine/threonine-protein kinase SRPK2 SRPK2 0.0013
1881 Hexokinase-1 HK1 0.0013
789 Alpha-1D adrenergic receptor ADRA1D 0.0013
760 Fibroblast growth factor 1 FGF1 0.0013
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0013
2371 Pantothenate kinase coaA 0.0013
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0013
3669 Ribokinase rbsK 0.0013
7 Nitric oxide synthase, inducible NOS2 0.0012
2950 Inositol-trisphosphate 3-kinase A ITPKA 0.0012
2892 Acetylglutamate kinase argB 0.0012
3550 Acetylglutamate kinase argB 0.0012
4366 Riboflavin kinase/FMN adenylyltransferase TM_0857 0.0012
825 Arsenical pump-driving ATPase ASNA1 0.0012
3435 Arsenical pump-driving ATPase arsA 0.0012
3639 Thymidine phosphorylase deoA 0.0012
3936 Thymidine phosphorylase TYMP 0.0012
1302 Dihydropyrimidine dehydrogenase [NADP+] DPYD 0.0012
137 FolC bifunctional protein [Includes: Folylpolyglutamate synthase folC 0.0012
2697 Uridine-cytidine kinase 2 UCK2 0.0012
6857 [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial PDK2 0.0012
2727 S-adenosylmethionine synthetase metK 0.0012
6259 (3R)-hydroxymyristoyl-acyl carrier protein dehydratase fabZ 0.0012
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0012
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0011
788 Creatine kinase M-type CKM 0.0011
6172 ATP-binding cassette sub-family B member 8, mitochondrial ABCB8 0.0011
2817 Phosphoribosylglycinamide formyltransferase 2 purT 0.0011
632 Alpha-1B adrenergic receptor ADRA1B 0.0011
6390 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 ATP2A1 0.0011
453 S-adenosylmethionine synthetase isoform type-1 MAT1A 0.0011
2404 Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform PIK3CG 0.0011
48 Pyridoxal kinase PDXK 0.0011
489 Monocarboxylate transporter 2 SLC16A7 0.0011
2240 Cell division protein kinase 2 CDK2 0.0011
2251 Thymidylate kinase tmk 0.0011
2254 Thymidylate kinase DTYMK 0.0011
3522 Thymidylate kinase tmk 0.0011
61 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0011
2644 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0011
2710 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0011
1524 Peptidyl-prolyl cis-trans isomerase A PPIA 0.0011
6700 Peptidyl-prolyl cis-trans isomerase A ppiA 0.0011
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0011
3587 Gastrotropin FABP6 0.0011
207 Glutathione synthetase GSS 0.001
5269 Glutathione synthetase gshB 0.001
2334 Dethiobiotin synthetase bioD 0.001
6555 Dethiobiotin synthetase bioD 0.001
5818 Folate receptor alpha FOLR1 0.001
833 Organic cation/carnitine transporter 1 SLC22A4 0.001
2091 Endoplasmin HSP90B1 0.001
556 Alpha-1A adrenergic receptor ADRA1A 0.001
6149 Solute carrier family 22 member 10 SLC22A10 0.001
1192 Sulfotransferase 1A1 SULT1A1 0.001
84 Nuclear receptor 0B1 NR0B1 0.001
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.001
467 Delta-type opioid receptor OPRD1 0.001
2511 MAP kinase-activated protein kinase 2 MAPKAPK2 0.001
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.001
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.001
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.001
696 Kappa-type opioid receptor OPRK1 0.001
6168 Solute carrier family 22 member 16 SLC22A16 0.001
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.001
2317 UDP-N-acetylmuramoylalanine--D-glutamate ligase murD 0.001
509 Thymidine kinase TK 0.001
570 Thymidine kinase TK 0.001
2559 Thymidine kinase TK 0.001
3430 Thymidine kinase tdk 0.001
3518 Thymidine kinase TK 0.001
5301 Thymidine kinase tdk 0.001
5771 Thymidine kinase ORF36 0.001
7009 Thymidine kinase ORF36 0.001
6395 Myosin-14 MYH14 0.0009
847 Mu-type opioid receptor OPRM1 0.0009
6014 Cytochrome P450 2A13 CYP2A13 0.0009
1422 Serine/threonine-protein kinase 6 AURKA 0.0009
3379 Kinesin-like protein KIF11 KIF11 0.0009
3456 Heat shock protein HSP 90-beta HSP90AB1 0.0009
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0009
3822 Actin, alpha skeletal muscle ACTA1 0.0009
380 Cytochrome P450 17A1 CYP17A1 0.0008
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0008
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0008
5682 Ribonuclease pancreatic RNASE1 0.0008
1721 Glycogen synthase kinase-3 beta GSK3B 0.0008
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0008
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0008
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0008
6085 Fatty acid-binding protein, intestinal FABP2 0.0008
1939 Heat shock protein HSP 90-alpha HSP90AA1 0.0007
76 Nitric-oxide synthase, brain NOS1 0.0007
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0007
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0007
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0006
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0006
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0006
6020 Aldehyde oxidase AOX1 0.0006
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0006
146 Androgen receptor AR 0.0006
291 Nitric-oxide synthase, endothelial NOS3 0.0006
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0006
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0006
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0006
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0006
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0006
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0005
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0005
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0005
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0005
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0005
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