Solute carrier family 22 member 2
Details
- Name
- Solute carrier family 22 member 2
- Synonyms
- hOCT2
- OCT2
- Organic cation transporter 2
- Gene Name
- SLC22A2
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0037250|Solute carrier family 22 member 2 MPTTVDDVLEHGGEFHFFQKQMFFLLALLSATFAPIYVGIVFLGFTPDHRCRSPGVAELS LRCGWSPAEELNYTVPGPGPAGEASPRQCRRYEVDWNQSTFDCVDPLASLDTNRSRLPLG PCRDGWVYETPGSSIVTEFNLVCANSWMLDLFQSSVNVGFFIGSMSIGYIADRFGRKLCL LTTVLINAAAGVLMAISPTYTWMLIFRLIQGLVSKAGWLIGYILITEFVGRRYRRTVGIF YQVAYTVGLLVLAGVAYALPHWRWLQFTVSLPNFFFLLYYWCIPESPRWLISQNKNAEAM RIIKHIAKKNGKSLPASLQRLRLEEETGKKLNPSFLDLVRTPQIRKHTMILMYNWFTSSV LYQGLIMHMGLAGDNIYLDFFYSALVEFPAAFMIILTIDRIGRRYPWAASNMVAGAACLA SVFIPGDLQWLKIIISCLGRMGITMAYEIVCLVNAELYPTFIRNLGVHICSSMCDIGGII TPFLVYRLTNIWLELPLMVFGVLGLVAGGLVLLLPETKGKALPETIEEAENMQRPRKNKE KMIYLQVQKLDIPLN
- Number of residues
- 555
- Molecular Weight
- 62579.99
- Theoretical pI
- 8.45
- GO Classification
- Functionscholine transmembrane transporter activity / dopamine transmembrane transporter activity / organic cation transmembrane transporter activity / quaternary ammonium group transmembrane transporter activityProcessesammonium transmembrane transport / body fluid secretion / choline transport / dopamine transport / drug transmembrane transport / neurotransmitter biosynthetic process / neurotransmitter secretion / organic cation transport / quaternary ammonium group transport / small molecule metabolic process / synaptic transmission / transmembrane transportComponentsextracellular exosome / integral component of plasma membrane / membrane / plasma membrane
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
- Pfam Domain Function
- Sugar_tr (PF00083)
- Transmembrane Regions
- 23-43 151-171 178-198 209-229 239-259 264-284 349-369 376-396 415-435 442-462 465-485 495-515
- Cellular Location
- Membrane
- Gene sequence
>lcl|BSEQ0012536|Solute carrier family 22 member 2 (SLC22A2) ATGCCCACCACCGTGGACGATGTCCTGGAGCATGGAGGGGAGTTTCACTTTTTCCAGAAG CAAATGTTTTTCCTCTTGGCTCTGCTCTCGGCTACCTTCGCGCCCATCTACGTGGGCATC GTCTTCCTGGGCTTCACCCCTGACCACCGCTGCCGGAGCCCCGGAGTGGCCGAGCTGAGT CTGCGCTGCGGCTGGAGTCCTGCAGAGGAACTGAACTACACGGTGCCGGGCCCAGGACCT GCGGGCGAAGCCTCCCCAAGACAGTGTAGGCGCTACGAGGTGGACTGGAACCAGAGCACC TTCGACTGCGTGGACCCCCTGGCCAGCCTGGACACCAACAGGAGCCGCCTGCCACTGGGC CCCTGCCGGGACGGCTGGGTGTACGAGACGCCTGGCTCGTCCATCGTCACCGAGTTTAAC CTGGTATGTGCCAACTCCTGGATGTTGGACCTATTCCAGTCATCAGTGAATGTAGGATTC TTTATTGGCTCTATGAGTATCGGCTACATAGCAGACAGGTTTGGCCGTAAGCTCTGCCTC CTAACTACAGTCCTCATAAATGCTGCAGCTGGAGTTCTCATGGCCATTTCCCCAACCTAT ACGTGGATGTTAATTTTTCGCTTAATCCAAGGACTGGTCAGCAAAGCAGGCTGGTTAATA GGCTACATCCTGATTACAGAATTTGTTGGGCGGAGATATCGGAGAACAGTGGGGATTTTT TACCAAGTTGCCTATACAGTTGGGCTCCTGGTGCTAGCTGGGGTGGCTTACGCACTTCCT CACTGGAGGTGGTTGCAGTTCACAGTTTCTCTGCCCAACTTCTTCTTCTTGCTCTATTAC TGGTGCATACCTGAGTCTCCCAGGTGGCTGATCTCCCAGAATAAGAATGCTGAAGCCATG AGAATCATTAAGCACATCGCAAAGAAAAATGGAAAATCTCTACCCGCCTCCCTTCAGCGC CTGAGACTTGAAGAGGAAACTGGCAAGAAATTGAACCCTTCATTTCTTGACTTGGTCAGA ACTCCTCAGATAAGGAAACATACTATGATATTGATGTACAACTGGTTCACGAGCTCTGTG CTCTACCAGGGCCTCATCATGCACATGGGCCTTGCAGGTGACAATATCTACCTGGATTTC TTCTACTCTGCCCTGGTTGAATTCCCAGCTGCCTTCATGATCATCCTCACCATCGACCGC ATCGGACGCCGTTACCCTTGGGCTGCATCAAATATGGTTGCAGGGGCAGCCTGTCTGGCC TCAGTTTTTATACCTGGTGATCTACAATGGCTAAAAATTATTATCTCATGCTTGGGAAGA ATGGGGATCACAATGGCCTATGAGATAGTCTGCCTGGTCAATGCTGAGCTGTACCCCACA TTCATTAGGAATCTTGGCGTCCACATCTGTTCCTCAATGTGTGACATTGGTGGCATCATC ACGCCATTCCTGGTCTACCGGCTCACTAACATCTGGCTTGAGCTCCCGCTGATGGTTTTC GGCGTGCTTGGCTTGGTTGCTGGAGGTCTGGTGCTGTTGCTTCCAGAAACTAAAGGGAAA GCTTTGCCTGAGACCATCGAGGAAGCCGAAAATATGCAAAGACCAAGAAAAAATAAAGAA AAGATGATTTACCTCCAAGTTCAGAAACTAGACATTCCATTGAACTAA
- Chromosome Location
- 6
- Locus
- 6q26
- External Identifiers
Resource Link UniProtKB ID O15244 UniProtKB Entry Name S22A2_HUMAN GenBank Protein ID 2281942 GenBank Gene ID X98333 HGNC ID HGNC:10966 - General References
- Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. [Article]
- Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [Article]
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- Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [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]
- Grundemann D, Schomig E: Gene structures of the human non-neuronal monoamine transporters EMT and OCT2. Hum Genet. 2000 Jun;106(6):627-35. [Article]
- Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H: Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52. [Article]
- Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [Article]
- Motohashi H, Sakurai Y, Saito H, Masuda S, Urakami Y, Goto M, Fukatsu A, Ogawa O, Inui K: Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol. 2002 Apr;13(4):866-74. [Article]
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Motohashi H, Uwai Y, Hiramoto K, Okuda M, Inui K: Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30. [Article]
- Ciarimboli G, Ludwig T, Lang D, Pavenstadt H, Koepsell H, Piechota HJ, Haier J, Jaehde U, Zisowsky J, Schlatter E: Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84. [Article]
- Kimura N, Masuda S, Tanihara Y, Ueo H, Okuda M, Katsura T, Inui K: Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86. [Article]
- Tahara H, Kusuhara H, Endou H, Koepsell H, Imaoka T, Fuse E, Sugiyama Y: A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45. Epub 2005 Jul 8. [Article]
- Kimura N, Okuda M, Inui K: Metformin transport by renal basolateral organic cation transporter hOCT2. Pharm Res. 2005 Feb;22(2):255-9. [Article]
- Biermann J, Lang D, Gorboulev V, Koepsell H, Sindic A, Schroter R, Zvirbliene A, Pavenstadt H, Schlatter E, Ciarimboli G: Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am J Physiol Cell Physiol. 2006 Jun;290(6):C1521-31. Epub 2006 Jan 4. [Article]
- Zhang S, Lovejoy KS, Shima JE, Lagpacan LL, Shu Y, Lapuk A, Chen Y, Komori T, Gray JW, Chen X, Lippard SJ, Giacomini KM: Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57. doi: 10.1158/0008-5472.CAN-06-0769. [Article]
- Okuda M, Kimura N, Inui K: Interactions of fluoroquinolone antibacterials, DX-619 and levofloxacin, with creatinine transport by renal organic cation transporter hOCT2. Drug Metab Pharmacokinet. 2006 Oct;21(5):432-6. [Article]
- Yonezawa A, Masuda S, Yokoo S, Katsura T, Inui K: Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86. Epub 2006 Aug 16. [Article]
- Yokoo S, Yonezawa A, Masuda S, Fukatsu A, Katsura T, Inui K: Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity. Biochem Pharmacol. 2007 Aug 1;74(3):477-87. Epub 2007 Mar 12. [Article]
- Bottalico B, Noskova V, Pilka R, Larsson I, Domanski H, Casslen B, Hansson SR: The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua. Mol Reprod Dev. 2007 Oct;74(10):1303-11. [Article]
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Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00571 Propranolol approved, investigational unknown inhibitor Details DB01580 Oxprenolol approved unknown inhibitor Details DB00264 Metoprolol approved, investigational unknown inhibitor Details DB00468 Quinine approved unknown inhibitor Details DB00122 Choline approved, nutraceutical unknown substrateinhibitor Details DB00917 Dinoprostone approved unknown inhibitor Details DB00152 Thiamine approved, investigational, nutraceutical, vet_approved unknown inhibitor Details DB00908 Quinidine approved, investigational unknown inhibitor Details DB01035 Procainamide approved unknown inhibitor Details DB00368 Norepinephrine approved unknown substrateinhibitor Details DB00184 Nicotine approved unknown inhibitor Details DB01137 Levofloxacin approved, investigational unknown inhibitor Details DB00458 Imipramine approved unknown inhibitor Details DB05381 Histamine approved, investigational unknown substrateinhibitor Details DB00536 Guanidine approved unknown inhibitor Details DB00365 Grepafloxacin approved, investigational, withdrawn unknown inhibitor Details DB00988 Dopamine approved unknown substrateinhibitor Details DB00501 Cimetidine approved, investigational unknown substrateinhibitor Details DB00915 Amantadine approved unknown substrateinhibitor Details DB00396 Progesterone approved, vet_approved unknown inhibitor Details DB00925 Phenoxybenzamine approved unknown inhibitor Details DB00783 Estradiol approved, investigational, vet_approved unknown inhibitordownregulator Details DB00914 Phenformin approved, investigational, withdrawn unknown inhibitor Details DB00331 Metformin approved unknown substrateinhibitor Details DB01151 Desipramine approved, investigational unknown inhibitor Details DB00927 Famotidine approved no inhibitor Details DB01032 Probenecid approved, investigational unknown inhibitor Details DB00345 Aminohippuric acid approved, investigational unknown inhibitor Details DB00907 Cocaine approved, illicit unknown inhibitor Details DB00515 Cisplatin approved unknown substrateinhibitor Details DB01103 Quinacrine investigational unknown inhibitor Details DB01114 Chlorpheniramine approved unknown inhibitor Details DB00594 Amiloride approved unknown inhibitor Details DB00668 Epinephrine approved, vet_approved unknown substrate Details DB00280 Disopyramide approved unknown inhibitor Details DB01075 Diphenhydramine approved, investigational unknown inhibitor Details DB00619 Imatinib approved no inhibitor Details DB05383 Pimagedine investigational unknown inhibitor Details DB01043 Memantine approved, investigational unknown substrate Details DB00413 Pramipexole approved, investigational unknown substrate Details DB00206 Reserpine approved, investigational, withdrawn unknown substrate Details DB00526 Oxaliplatin approved, investigational no substrate Details DB08837 Tetraethylammonium experimental, investigational unknown substrate Details DB08839 Serotonin investigational, nutraceutical unknown Details DB08840 N-methylnicotinamide experimental unknown Details DB00495 Zidovudine approved unknown Details DB08838 Agmatine experimental unknown substrate Details DB01199 Tubocurarine approved unknown Details DB01337 Pancuronium approved unknown Details DB01160 Dinoprost tromethamine approved, vet_approved unknown Details DB00690 Flurazepam approved, illicit, investigational unknown inhibitor Details DB00709 Lamivudine approved, investigational unknown substrate Details DB09555 Dexchlorpheniramine maleate approved unknown inhibitor Details DB12598 Nafamostat investigational unknown substrate Details DB13874 Enasidenib approved, investigational unknown inhibitor Details DB08930 Dolutegravir approved no inhibitor Details DB11817 Baricitinib approved, investigational unknown inhibitor Details DB13952 Estradiol acetate approved, investigational, vet_approved unknown inhibitor Details DB13953 Estradiol benzoate approved, investigational, vet_approved unknown inhibitor Details DB13954 Estradiol cypionate approved, investigational, vet_approved unknown inhibitor Details DB13955 Estradiol dienanthate approved, investigational, vet_approved unknown inhibitor Details DB13956 Estradiol valerate approved, investigational, vet_approved unknown inhibitor Details DB11901 Apalutamide approved, investigational no inhibitor Details DB11633 Isavuconazole approved, investigational unknown inhibitor Details DB14006 Choline salicylate approved, nutraceutical unknown substrateinhibitor Details DB00863 Ranitidine approved, withdrawn unknown substrate Details DB06608 Tafenoquine approved, investigational no inhibitor Details DB09078 Lenvatinib approved, investigational unknown inhibitor Details DB01273 Varenicline approved, investigational unknown substrateinhibitor Details DB01156 Bupropion approved unknown inhibitor Details DB06637 Dalfampridine approved unknown substrate Details DB01118 Amiodarone approved, investigational unknown inhibitor Details DB00758 Clopidogrel approved no inhibitor Details DB09343 Tipiracil approved, investigational unknown substrate Details DB00204 Dofetilide approved, investigational no substrate Details DB00555 Lamotrigine approved, investigational no inhibitor Details DB05294 Vandetanib approved no inhibitor Details DB00437 Allopurinol approved unknown Details DB14754 Solriamfetol approved unknown Details DB13946 Testosterone undecanoate approved, investigational unknown inducer Details DB08882 Linagliptin approved unknown substrateinhibitor Details DB12147 Erdafitinib approved, investigational no inhibitor Details DB00448 Lansoprazole approved, investigational unknown Details DB04855 Dronedarone approved no inhibitor Details DB12001 Abemaciclib approved, investigational unknown inhibitor Details DB15328 Ubrogepant approved, investigational unknown inhibitor Details DB01018 Guanfacine approved, investigational unknown substrate Details DB00938 Salmeterol approved unknown inhibitor Details DB12457 Rimegepant approved, investigational unknown inhibitor Details DB11837 Osilodrostat approved, investigational unknown inhibitor Details DB09241 Methylene blue approved, investigational unknown inhibitor Details DB11652 Tucatinib approved, investigational unknown inhibitor Details DB15102 Pemigatinib approved, investigational no inhibitor Details DB06137 Tirbanibulin approved, investigational no inhibitor Details DB15442 Trilaciclib approved, investigational unknown inhibitor Details DB00391 Sulpiride approved, investigational unknown substrate Details DB00871 Terbutaline approved unknown substrate Details DB00960 Pindolol approved, investigational unknown substrate Details DB08893 Mirabegron approved no substrate Details DB00986 Glycopyrronium approved, investigational, vet_approved unknown substrate Details DB00798 Gentamicin approved, vet_approved no substrate Details DB11886 Infigratinib approved, investigational no inhibitor Details DB12265 Fexinidazole approved, investigational unknown inhibitor Details DB06176 Romidepsin approved, investigational no inhibitor Details DB05667 Levoketoconazole approved, investigational no inhibitor Details DB11697 Pacritinib approved, investigational no inhibitor Details DB08912 Dabrafenib approved, investigational no inhibitor Details DB15133 Tepotinib approved, investigational no inhibitor Details DB11640 Amifampridine approved, investigational no inhibitor Details DB16267 Olutasidenib approved, investigational no inhibitor Details DB00363 Clozapine approved no Details DB11712 Tezacaftor approved, investigational no inhibitor Details DB09076 Umeclidinium approved no substrate Details DB11718 Encorafenib approved, investigational no inhibitor Details DB12218 Capivasertib approved, investigational no inhibitor Details