DT-Web

DB04941 - Crofelemer


Identification
Name Crofelemer
Accession Number DB04941
Type small molecule
Description Crofelemer, previously known as the investigational drug SP-303, is a novel proanthocyanidin purified from the bark latex of the Amazonian Croton tree Croton lechleri. It is marketed under the brand name Fulyzaq and indicated for the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight Not Available
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.
Mechanism of action Crofelemer is an inhibitor of the cystic fibrosis transmembrane regulator chloride channel (CFTR), as evidenced by its activity on cell cultures, single cell patch clamps, single CFTR channels, and elaboration of mouse intestinal fluid secretion. Crofelemer also inhibits calcium activated chloride channels (CaCC), which in combination with CFTR, are expressed on the luminal side of intestinal cells. Crofelemer inhibition of both of these channels prevents water loss from diarrhea by inhibiting chloride secretion.
Absorption The absorption of crofelemer is minimal and crofelemer concentrations in plasma are below the level of quantitation (50 ng/mL).
Protein binding Since crofelemer is not significantly absorbed, protein binding was not quantified.
Biotransformation Since crofelemer is not significantly absorbed, no metabolites have been identified.
Route of elimination Since crofelemer is not significantly absorbed, the route of elimination has not been identified.
Toxicity The most common adverse effects are cough, flatulence, upper respiratory tract infection, bronchitis, and increased bilirubin.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions
  • Crofelemer is not affected by food.

Targets


Cystic fibrosis transmembrane conductance regulator
Name Cystic fibrosis transmembrane conductance regulator
Gene Name CFTR
Pharmacological action yes
Actions antagonist
References
  • Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. - Pubmed
DTHybrid score 0.3203
Anoctamin-1
Name Anoctamin-1
Gene Name Not Available
Pharmacological action yes
Actions antagonist
References
  • Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
587 Serum albumin ALB 0.0262
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0232
1588 Multidrug resistance protein 1 ABCB1 0.022
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0177
53 Solute carrier family 12 member 5 SLC12A5 0.0171
663 Solute carrier family 12 member 4 SLC12A4 0.0171
4512 Cytochrome P450 3A4 CYP3A4 0.0167
310 Solute carrier family 12 member 2 SLC12A2 0.0158
1729 Solute carrier family 22 member 6 SLC22A6 0.0156
2514 Phosphocarrier protein HPr ptsH 0.0154
5689 Phosphocarrier protein HPr ptsH 0.0154
3602 Anti-sigma F factor antagonist spoIIAA 0.0154
5686 Potassium voltage-gated channel subfamily C member 4 KCNC4 0.0154
6143 Solute carrier family 22 member 7 SLC22A7 0.0145
1024 Solute carrier family 22 member 11 SLC22A11 0.0144
1130 Lithostathine 1 alpha REG1A 0.0134
4542 Glutaminase 1 glsA1 0.0134
4544 Glutaminase 1 glsA1 0.0134
4318 Siroheme synthase cysG 0.013
290 Prostaglandin G/H synthase 2 PTGS2 0.013
6142 Solute carrier family 22 member 8 SLC22A8 0.0126
3119 Fimbrial protein pilE1 0.0125
2530 Protein kinase C theta type PRKCQ 0.0123
558 Solute carrier family 12 member 1 SLC12A1 0.0122
6141 Sodium/bile acid cotransporter SLC10A1 0.0118
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.0117
3453 Alkaline phosphatase phoA 0.0116
5150 Endo-1,4-beta-xylanase Y xynY 0.0113
2503 Phosphomannomutase/phosphoglucomutase algC 0.011
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0108
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0104
2021 Thrombomodulin THBD 0.01
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0092
2180 3-phosphoinositide-dependent protein kinase 1 PDPK1 0.0091
862 Multidrug resistance-associated protein 1 ABCC1 0.0091
10 Glycogen phosphorylase, liver form PYGL 0.0091
2207 Rhodopsin RHO 0.009
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0084
5646 Galactokinase GALK1 0.0081
3390 Aminoglycoside 3'-phosphotransferase aphA 0.0081
6029 Aminoglycoside 3'-phosphotransferase aphA1 0.0081
5302 TrwB trwB 0.0081
5265 FtsH ftsH 0.0081
1792 Tissue-type plasminogen activator PLAT 0.0074
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0073
5312 Kinesin-like protein KIF1A KIF1A 0.0073
6085 Fatty acid-binding protein, intestinal FABP2 0.0072
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0072
273 Apoptosis regulator Bcl-2 BCL2 0.0072
1152 Glycogen phosphorylase, muscle form PYGM 0.007
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0069
6016 Cytochrome P450 2C19 CYP2C19 0.0068
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0068
2892 Acetylglutamate kinase argB 0.0068
3550 Acetylglutamate kinase argB 0.0068
2371 Pantothenate kinase coaA 0.0068
2615 Chemotaxis protein cheA cheA 0.0068
2950 Inositol-trisphosphate 3-kinase A ITPKA 0.0067
825 Arsenical pump-driving ATPase ASNA1 0.0067
3435 Arsenical pump-driving ATPase arsA 0.0067
1881 Hexokinase-1 HK1 0.0067
6832 Serine/threonine-protein kinase SRPK2 SRPK2 0.0065
4757 Cytochrome P450 2C9 CYP2C9 0.0065
2727 S-adenosylmethionine synthetase metK 0.0064
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0063
2817 Phosphoribosylglycinamide formyltransferase 2 purT 0.0061
4178 DNA repair protein RAD51 homolog 1 RAD51 0.006
5643 General secretion pathway protein E epsE 0.006
3794 Osmolarity sensor protein envZ envZ 0.006
5644 Sensor protein phoQ phoQ 0.006
5641 Rod shape-determining protein MreB TM_0588 0.006
5649 Potassium-transporting ATPase B chain kdpB 0.0059
5642 Chaperone clpB clpB 0.0059
5645 DNA topoisomerase 4 subunit B parE 0.0059
6227 DNA topoisomerase 4 subunit B parE 0.0059
207 Glutathione synthetase GSS 0.0057
5269 Glutathione synthetase gshB 0.0057
2251 Thymidylate kinase tmk 0.0056
2254 Thymidylate kinase DTYMK 0.0056
3522 Thymidylate kinase tmk 0.0056
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0053
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0052
740 Argininosuccinate synthase ASS1 0.0052
865 Argininosuccinate synthase ASS1 0.0052
2680 Argininosuccinate synthase argG 0.0052
3194 Argininosuccinate synthase argG 0.0052
4751 Mitogen-activated protein kinase 12 MAPK12 0.0052
2867 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase ispE 0.0052
2852 DNA mismatch repair protein mutL mutL 0.0052
2397 Dihydroxyacetone kinase dhaK 0.0052
6433 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 PFKFB4 0.0052
3822 Actin, alpha skeletal muscle ACTA1 0.0051
776 Bile salt export pump ABCB11 0.0051
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0051
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.005
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0049
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0049
3231 Death-associated protein kinase 1 DAPK1 0.0049
4373 Medium-chain-fatty-acid--CoA ligase Not Available 0.0048
2299 UDP-N-acetylmuramate--L-alanine ligase murC 0.0048
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0048
1721 Glycogen synthase kinase-3 beta GSK3B 0.0048
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0047
2164 Multidrug resistance-associated protein 4 ABCC4 0.0046
936 Ephrin type-A receptor 2 EPHA2 0.0046
887 DNA gyrase subunit B gyrB 0.0046
4150 DNA gyrase subunit B gyrB 0.0046
6225 DNA gyrase subunit B gyrB 0.0046
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0044
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0044
958 Insulin-like growth factor 1 receptor IGF1R 0.0043
20 Prostaglandin G/H synthase 1 PTGS1 0.0039
4192 DNA topoisomerase 2-beta TOP2B 0.0039
937 Proto-oncogene tyrosine-protein kinase LCK LCK 0.0036
1836 Mitogen-activated protein kinase 10 MAPK10 0.0034
4924 Cytochrome P450 2C8 CYP2C8 0.0034
2236 Casein kinase II subunit alpha CSNK2A1 0.0032
5287 Signaling protein Not Available 0.003
5288 Shikimate kinase aroK 0.003
5314 UPF0079 ATP-binding protein HI0065 HI_0065 0.003
5304 UPF0166 protein TM_0021 TM_0021 0.003
3199 Phosphopantetheine adenylyltransferase coaD 0.003
3543 Phosphopantetheine adenylyltransferase coaD 0.003
3567 Phosphopantetheine adenylyltransferase coaD 0.003
5289 Phosphopantetheine adenylyltransferase coaD 0.003
4346 Polynucleotide kinase pseT 0.003
5293 Shikimate kinase 2 aroL 0.003
5283 D-alanine--D-alanine ligase B ddlB 0.003
5281 Plasmid segregation protein parM parM 0.003
5305 Phosphoribosylaminoimidazole carboxylase ATPase subunit purK 0.003
5292 Putative partitioning protein TT_C1605 0.003
5276 Chromosomal replication initiator protein dnaA dnaA 0.003
5266 Activator of hgdC 0.003
5290 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.003
5638 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.003
5270 ATP-dependent Clp protease ATP-binding subunit clpX clpX 0.003
2874 Nitrogenase iron protein 1 nifH1 0.003
5299 D-alanine--D-alanine ligase ddl 0.003
6598 D-alanine--D-alanine ligase ddl 0.003
5275 Multidrug resistance ABC transporter ATP-binding and permease protein lmrA 0.003
1549 Heat shock 70 kDa protein 1 HSPA1A 0.003
5308 Preprotein translocase secA 1 subunit secA1 0.003
5259 Transcriptional regulator ntrC1 0.003
6699 Transcriptional regulator Cgl2612 0.003
5284 Large T antigen Not Available 0.003
5291 Glycogen synthase 1 glgA1 0.003
3777 ATP-dependent Clp protease ATP-binding subunit clpA clpA 0.003
5264 DNA replication protein REP 0.003
5277 Preprotein translocase subunit secA secA 0.003
4794 Phosphoenolpyruvate carboxykinase [ATP] pckA 0.003
5285 Kinesin heavy chain KIF5B 0.003
5315 Chaperone protein htpG htpG 0.003
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.003
5261 Phosphoribosylformylglycinamidine synthase purL 0.003
3470 Hypothetical protein MG245 homolog MPN_348 0.0025
6277 Heat shock cognate 71 kDa protein HSPA8 0.0025
3426 Glutamine synthetase glnA 0.0025
3987 Glutamine synthetase GLUL 0.0025
3175 Glutamate--cysteine ligase gshA 0.0025
5295 2-keto-3-deoxy-gluconate kinase TT_P0036 0.0025
5189 Trimethylamine dehydrogenase tmd 0.0025
2751 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0025
4755 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0025
4106 Guanylate kinase GUK1 0.0025
4516 Guanylate kinase gmk 0.0025
2270 Dephospho-CoA kinase coaE 0.0024
413 Amidophosphoribosyltransferase PPAT 0.0024
2515 Amidophosphoribosyltransferase purF 0.0024
3714 Amidophosphoribosyltransferase purF 0.0024
4837 Cag-alfa cag-alfa 0.0024
4774 NTPase P4 Not Available 0.0024
4838 PMS1 protein homolog 2 PMS2 0.0024
2284 Adenylate kinase adk 0.0024
2296 Adenylate kinase adk 0.0024
2311 Adenylate kinase adk 0.0024
2312 Adenylate kinase Not Available 0.0024
4839 DNA polymerase III subunit tau dnaX 0.0024
2683 Mono-ADP-ribosyltransferase C3 C3 0.0023
340 Apoptotic protease-activating factor 1 APAF1 0.0023
5300 Antigen peptide transporter 1 TAP1 0.0023
5271 Focal adhesion kinase 1 PTK2 0.0022
2390 Nonsecretory ribonuclease RNASE2 0.0022
2922 Glycerol kinase glpK 0.0022
2282 Protein recA recA 0.0021
2315 Protein recA recA 0.0021
2332 Protein recA recA 0.0021
5263 Protein recA recA 0.0021
408 Riboflavin kinase RFK 0.0021
6857 [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial PDK2 0.0021
4366 Riboflavin kinase/FMN adenylyltransferase TM_0857 0.0021
5278 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 PAPSS1 0.002
3669 Ribokinase rbsK 0.002
137 FolC bifunctional protein [Includes: Folylpolyglutamate synthase folC 0.002
788 Creatine kinase M-type CKM 0.002
6390 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 ATP2A1 0.002
2334 Dethiobiotin synthetase bioD 0.0019
6555 Dethiobiotin synthetase bioD 0.0019
2697 Uridine-cytidine kinase 2 UCK2 0.0019
453 S-adenosylmethionine synthetase isoform type-1 MAT1A 0.0018
61 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0018
2644 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0018
2710 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0018
48 Pyridoxal kinase PDXK 0.0018
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0018
2511 MAP kinase-activated protein kinase 2 MAPKAPK2 0.0018
2317 UDP-N-acetylmuramoylalanine--D-glutamate ligase murD 0.0017
6395 Myosin-14 MYH14 0.0017
702 UMP-CMP kinase CMPK1 0.0017
2091 Endoplasmin HSP90B1 0.0017
1422 Serine/threonine-protein kinase 6 AURKA 0.0016
3379 Kinesin-like protein KIF11 KIF11 0.0016
3456 Heat shock protein HSP 90-beta HSP90AB1 0.0016
504 Mast/stem cell growth factor receptor KIT 0.0016
509 Thymidine kinase TK 0.0015
570 Thymidine kinase TK 0.0015
2559 Thymidine kinase TK 0.0015
3430 Thymidine kinase tdk 0.0015
3518 Thymidine kinase TK 0.0015
5301 Thymidine kinase tdk 0.0015
5771 Thymidine kinase ORF36 0.0015
7009 Thymidine kinase ORF36 0.0015
5294 Nucleoside diphosphate kinase A NME1 0.0015
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0014
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0014
4773 Deoxycytidine kinase DCK 0.0014
5682 Ribonuclease pancreatic RNASE1 0.0013
1939 Heat shock protein HSP 90-alpha HSP90AA1 0.0012
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