Cytochrome P450 2A6
Details
- Name
- Cytochrome P450 2A6
- Kind
- protein
- Synonyms
- 1,4-cineole 2-exo-monooxygenase
- 1.14.14.-
- Coumarin 7-hydroxylase
- CYP2A3
- CYPIIA6
- Cytochrome P450 IIA3
- Cytochrome P450(I)
- Gene Name
- CYP2A6
- UniProtKB Entry
- P11509Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0055966|Cytochrome P450 2A6 MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMK ISERYGPVFTIHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSN GERAKQLRRFSIATLRDFGVGKRGIEERIQEEAGFLIDALRGTGGANIDPTFFLSRTVSN VISSIVFGDRFDYKDKEFLSLLRMMLGIFQFTSTSTGQLYEMFSSVMKHLPGPQQQAFQL LQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFI GGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYMEAVIHEIQ RFGDVIPMSLARRVKKDTKFRDFFLPKGTEVYPMLGSVLRDPSFFSNPQDFNPQHFLNEK GQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGF ATIPRNYTMSFLPR
- Number of residues
- 494
- Molecular Weight
- 56517.005
- Theoretical pI
- 9.69
- GO Classification
- Functionsarachidonic acid epoxygenase activity / coumarin 7-hydroxylase activity / enzyme binding / heme binding / iron ion binding / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenProcessescoumarin catabolic process / coumarin metabolic process / epoxygenase P450 pathway / steroid metabolic process / xenobiotic metabolic processComponentscytoplasm / cytoplasmic microtubule / endoplasmic reticulum membrane / intracellular membrane-bounded organelle
- General Function
- Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
- Specific Function
- arachidonic acid epoxygenase activity
- Pfam Domain Function
- p450 (PF00067)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Endoplasmic reticulum membrane
- Gene sequence
>lcl|BSEQ0021356|Cytochrome P450 2A6 (CYP2A6) ATGCTGGCCTCAGGGATGCTTCTGGTGGCCTTGCTGGTCTGCCTGACTGTAATGGTCTTG ATGTCTGTTTGGCAGCAGAGGAAGAGCAAGGGGAAGCTGCCTCCGGGACCCACCCCATTG CCCTTCATTGGAAACTACCTGCAGCTGAACACAGAGCAGATGTACAACTCCCTCATGAAG ATCAGTGAGCGCTATGGCCCCGTGTTCACCATTCACTTGGGGCCCCGGCGGGTCGTGGTG CTGTGTGGACATGATGCCGTCAGGGAGGCTCTGGTGGACCAGGCTGAGGAGTTCAGCGGG CGAGGCGAGCAAGCCACCTTCGACTGGGTCTTCAAAGGCTATGGCGTGGTATTCAGCAAC GGGGAGCGCGCCAAGCAGCTCCGGCGCTTCTCCATCGCCACCCTGCGGGACTTCGGGGTG GGCAAGCGAGGCATCGAGGAGCGCATCCAGGAGGAGGCGGGCTTCCTCATCGACGCCCTC CGGGGCACTGGCGGCGCCAATATCGATCCCACCTTCTTCCTGAGCCGCACAGTCTCCAAT GTCATCAGCTCCATTGTCTTTGGGGACCGCTTTGACTATAAGGACAAAGAGTTCCTGTCA CTGTTGCGCATGATGCTAGGAATCTTCCAGTTCACGTCAACCTCCACGGGGCAGCTCTAT GAGATGTTCTCTTCGGTGATGAAACACCTGCCAGGACCACAGCAACAGGCCTTTCAGTTG CTGCAAGGGCTGGAGGACTTCATAGCCAAGAAGGTGGAGCACAACCAGCGCACGCTGGAT CCCAATTCCCCACGGGACTTCATTGACTCCTTTCTCATCCGCATGCAGGAGGAGGAGAAG AACCCCAACACGGAGTTCTACTTGAAAAACCTGGTGATGACCACGTTGAACCTCTTCATT GGGGGCACCGAGACCGTCAGCACCACCCTGCGCTATGGCTTCTTGCTGCTCATGAAGCAC CCAGAGGTGGAGGCCAAGGTCCATGAGGAGATTGACAGAGTGATCGGCAAGAACCGGCAG CCCAAGTTTGAGGACCGGGCCAAGATGCCCTACATGGAGGCAGTGATCCACGAGATCCAA AGATTTGGAGACGTGATCCCCATGAGTTTGGCCCGCAGAGTCAAAAAGGACACCAAGTTT CGGGATTTCTTCCTCCCTAAGGGCACCGAAGTGTACCCTATGCTGGGCTCTGTGCTGAGA GACCCCAGTTTCTTCTCCAACCCCCAGGACTTCAATCCCCAGCACTTCCTGAATGAGAAG GGGCAGTTTAAGAAGAGTGATGCTTTTGTGCCCTTTTCCATCGGAAAGCGGAACTGTTTC GGAGAAGGCCTGGCCAGAATGGAGCTCTTTCTCTTCTTCACCACCGTCATGCAGAACTTC CGCCTCAAGTCCTCCCAGTCACCTAAGGACATTGACGTGTCCCCCAAACACGTGGGCTTT GCCACGATCCCACGAAACTACACCATGAGCTTCCTGCCCCGCTGA
- Chromosome Location
- 19
- Locus
- 19q13.2
- External Identifiers
Resource Link UniProtKB ID P11509 UniProtKB Entry Name CP2A6_HUMAN GenBank Gene ID X13897 GeneCard ID CYP2A6 GenAtlas ID CYP2A6 HGNC ID HGNC:2610 PDB ID(s) 1Z10, 1Z11, 2FDU, 2FDV, 2FDW, 2FDY, 3EBS, 3T3Q, 3T3R, 4EJJ, 4RUI KEGG ID hsa:1548 IUPHAR/Guide To Pharmacology ID 1321 NCBI Gene ID 1548 - General References
- Miles JS, Bickmore W, Brook JD, McLaren AW, Meehan R, Wolf CR: Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity. Nucleic Acids Res. 1989 Apr 25;17(8):2907-17. [Article]
- Yamano S, Nagata K, Yamazoe Y, Kato R, Gelboin HV, Gonzalez FJ: cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3). Nucleic Acids Res. 1989 Jun 26;17(12):4888. [Article]
- Yamano S, Tatsuno J, Gonzalez FJ: The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. Biochemistry. 1990 Feb 6;29(5):1322-9. [Article]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Maurice M, Emiliani S, Dalet-Beluche I, Derancourt J, Lange R: Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. Eur J Biochem. 1991 Sep 1;200(2):511-7. [Article]
- Yun CH, Shimada T, Guengerich FP: Purification and characterization of human liver microsomal cytochrome P-450 2A6. Mol Pharmacol. 1991 Nov;40(5):679-85. [Article]
- Kitagawa K, Kunugita N, Kitagawa M, Kawamoto T: CYP2A6*6, a novel polymorphism in cytochrome p450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity. J Biol Chem. 2001 May 25;276(21):17830-5. Epub 2001 Feb 16. [Article]
- Phillips IR, Shephard EA, Ashworth A, Rabin BR: Isolation and sequence of a human cytochrome P-450 cDNA clone. Proc Natl Acad Sci U S A. 1985 Feb;82(4):983-7. [Article]
- Miyazawa M, Shindo M, Shimada T: Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica. 2001 Oct;31(10):713-23. [Article]
- Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
- Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF: Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol. 2005 Sep;12(9):822-3. Epub 2005 Aug 7. [Article]
- Yano JK, Denton TT, Cerny MA, Zhang X, Johnson EF, Cashman JR: Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization. J Med Chem. 2006 Nov 30;49(24):6987-7001. [Article]
- DeVore NM, Smith BD, Urban MJ, Scott EE: Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes. Drug Metab Dispos. 2008 Dec;36(12):2582-90. doi: 10.1124/dmd.108.023770. Epub 2008 Sep 8. [Article]
- Hadidi H, Zahlsen K, Idle JR, Cholerton S: A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin. Food Chem Toxicol. 1997 Sep;35(9):903-7. [Article]
- Oscarson M, McLellan RA, Gullsten H, Agundez JA, Benitez J, Rautio A, Raunio H, Pelkonen O, Ingelman-Sundberg M: Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. FEBS Lett. 1999 Oct 29;460(2):321-7. [Article]
- Ariyoshi N, Sawamura Y, Kamataki T: A novel single nucleotide polymorphism altering stability and activity of CYP2a6. Biochem Biophys Res Commun. 2001 Mar 2;281(3):810-4. [Article]
- Kiyotani K, Fujieda M, Yamazaki H, Shimada T, Guengerich FP, Parkinson A, Nakagawa K, Ishizaki T, Kamataki T: Twenty one novel single nucleotide polymorphisms (SNPs) of the CYP2A6 gene in Japanese and Caucasians. Drug Metab Pharmacokinet. 2002;17(5):482-7. [Article]
- Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y: Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population. J Hum Genet. 2003;48(5):249-70. Epub 2003 Apr 29. [Article]
- Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP: Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004 Oct;5(7):895-931. [Article]
- Mwenifumbo JC, Al Koudsi N, Ho MK, Zhou Q, Hoffmann EB, Sellers EM, Tyndale RF: Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent. Hum Mutat. 2008 May;29(5):679-88. doi: 10.1002/humu.20698. [Article]
- Ho MK, Mwenifumbo JC, Zhao B, Gillam EM, Tyndale RF: A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent. Pharmacogenet Genomics. 2008 Jan;18(1):67-75. doi: 10.1097/FPC.0b013e3282f3606e. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Coumarin experimental unknown target Details Nicotine approved unknown enzyme substrateinhibitor Details Letrozole approved, investigational unknown enzyme substrateinhibitor Details Chlorzoxazone approved unknown enzyme substrate Details Methoxsalen approved unknown enzyme inhibitor Details Tranylcypromine approved, investigational unknown enzyme inhibitor Details Metyrapone approved, investigational unknown enzyme inhibitor Details Pilocarpine approved, investigational unknown enzyme substrateinhibitor Details Halothane approved, vet_approved unknown enzyme substrate Details Plitidepsin investigational unknown enzyme substrate Details Nifedipine approved unknown enzyme substrate Details Selegiline approved, investigational, vet_approved unknown enzyme substrateinhibitor Details Ifosfamide approved unknown enzyme substrate Details Valproic acid approved, investigational unknown enzyme substrate Details Nevirapine approved unknown enzyme substrate Details Cinnarizine approved, investigational unknown enzyme substrate Details Flunarizine approved unknown enzyme substrate Details Montelukast approved unknown enzyme substrate Details N,N-DIMETHYL(5-(PYRIDIN-3-YL)FURAN-2-YL)METHANAMINE experimental unknown target Details N-METHYL(5-(PYRIDIN-3-YL)FURAN-2-YL)METHANAMINE experimental unknown target Details (5-(PYRIDIN-3-YL)FURAN-2-YL)METHANAMINE experimental unknown target Details 4,4'-DIPYRIDYL DISULFIDE experimental unknown target Details Amphetamine approved, illicit, investigational unknown enzyme inhibitor Details Azelastine approved unknown enzyme substrateinhibitor Details Cisapride approved, investigational, withdrawn unknown enzyme substrate Details Clomethiazole investigational unknown enzyme substrate Details Clotrimazole approved, vet_approved unknown enzyme inhibitor Details Clozapine approved no enzyme substrate Details Cyclophosphamide approved, investigational unknown enzyme substrate Details Dexamethasone approved, investigational, vet_approved unknown enzyme inducer Details Eletriptan approved, investigational unknown enzyme inducer Details Flunitrazepam approved, illicit unknown enzyme substrate Details Fluorouracil approved unknown enzyme substrate Details Fomepizole approved, vet_approved unknown enzyme inhibitor Details Isoniazid approved, investigational unknown enzyme inhibitor Details Ketoconazole approved, investigational unknown enzyme inhibitor Details Lidocaine approved, vet_approved unknown enzyme substrate Details Memantine approved, investigational unknown enzyme inhibitor Details Menadione approved, nutraceutical unknown enzyme inhibitor Details Methoxyflurane approved, investigational, vet_approved, withdrawn unknown enzyme substrate Details Miconazole approved, investigational, vet_approved unknown enzyme inhibitor Details Nilvadipine approved, investigational unknown enzyme inhibitor Details Acetaminophen approved unknown enzyme substrate Details Phenacetin withdrawn unknown enzyme substrate Details Antipyrine approved, investigational unknown enzyme substrate Details Phenobarbital approved, investigational unknown enzyme inducer Details Progesterone approved, vet_approved unknown enzyme inducer Details Rifampin approved unknown enzyme inducer Details Seratrodast experimental unknown enzyme inhibitor Details Sevoflurane approved, vet_approved unknown enzyme substrate Details Tamoxifen approved unknown enzyme substrate Details Methimazole approved unknown enzyme inhibitor Details Zidovudine approved unknown enzyme substrate Details Flurazepam approved, illicit, investigational unknown enzyme substrate Details Tretinoin approved, investigational, nutraceutical unknown enzyme substrate Details Arformoterol approved, investigational unknown enzyme substrate Details Lorcaserin approved, withdrawn no enzyme substrate Details Amiodarone approved, investigational unknown enzyme inhibitor Details Pentobarbital approved, investigational, vet_approved unknown enzyme inducer Details Dapagliflozin approved no enzyme substrate Details Vortioxetine approved, investigational no enzyme substrate Details Tegafur approved, investigational no enzyme substrate Details Tegafur-uracil approved, investigational no enzyme substrate Details Asunaprevir approved, investigational, withdrawn no enzyme substrate Details Artesunate approved, investigational unknown enzyme substrate Details Triclabendazole approved, investigational unknown enzyme inhibitor Details Metronidazole approved unknown enzyme substrate Details Apremilast approved, investigational unknown enzyme substrate Details Fenofibrate approved unknown enzyme inhibitor Details Norethisterone approved unknown enzyme substrate Details Prednisone approved, vet_approved unknown enzyme inducer Details Hydrocortisone approved, vet_approved unknown enzyme inducer Details Cenobamate approved, investigational unknown enzyme substrate Details Budesonide approved unknown enzyme inducer Details Methylprednisolone approved, vet_approved unknown enzyme inducer Details Phenytoin approved, vet_approved no enzyme substrate Details Formoterol approved, investigational unknown enzyme substrate Details Betamethasone approved, vet_approved unknown enzyme inducer Details Prednisolone phosphate approved, vet_approved unknown enzyme inducer Details Dexamethasone acetate approved, investigational, vet_approved unknown enzyme inducer Details Lonafarnib approved, investigational no enzyme substrate Details Ethambutol approved unknown enzyme inhibitor Details Ropeginterferon alfa-2b approved, investigational no enzyme inhibitor Details Cannabidiol approved, investigational unknown enzyme inhibitor Details Dronabinol approved, illicit no enzyme inhibitor Details Cannabinol experimental, investigational unknown enzyme inhibitor Details Medical Cannabis experimental, investigational unknown enzyme inhibitor Details Terpinen-4-ol investigational no enzyme substrate Details Elacestrant approved, investigational unknown enzyme substrate Details Brinzolamide approved no enzyme substrate Details Methoxsalen approved yes target binder Details