AY7

asciminib

Created:	2016-12-13
Last modified:	2017-04-02

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2 entries where AY7 is found as a standalone ligand

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Chemical Details
Formal Charge	0
Atom Count	49
Chiral Atom Count	1
Bond Count	52
Aromatic Bond Count	17

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Chemical Component Summary
Name	asciminib
Systematic Name (OpenEye OEToolkits)	~{N}-[4-[chloranyl-bis(fluoranyl)methoxy]phenyl]-6-[(3~{R})-3-oxidanylpyrrolidin-1-yl]-5-(1~{H}-pyrazol-5-yl)pyridine-3-carboxamide
Formula	C₂₀ H₁₈ Cl F₂ N₅ O₃
Molecular Weight	449.838
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	CACTVS	3.385	O[CH]1CCN(C1)c2ncc(cc2c3[nH]ncc3)C(=O)Nc4ccc(OC(F)(F)Cl)cc4
SMILES	OpenEye OEToolkits	2.0.6	c1cc(ccc1NC(=O)c2cc(c(nc2)N3CCC(C3)O)c4ccn[nH]4)OC(F)(F)Cl
Canonical SMILES	CACTVS	3.385	O[C@@H]1CCN(C1)c2ncc(cc2c3[nH]ncc3)C(=O)Nc4ccc(OC(F)(F)Cl)cc4
Canonical SMILES	OpenEye OEToolkits	2.0.6	c1cc(ccc1NC(=O)c2cc(c(nc2)N3CC[C@H](C3)O)c4ccn[nH]4)OC(F)(F)Cl
InChI	InChI	1.03	InChI=1S/C20H18ClF2N5O3/c21-20(22,23)31-15-3-1-13(2-4-15)26-19(30)12-9-16(17-5-7-25-27-17)18(24-10-12)28-8-6-14(29)11-28/h1-5,7,9-10,14,29H,6,8,11H2,(H,25,27)(H,26,30)/t14-/m1/s1
InChIKey	InChI	1.03	VOVZXURTCKPRDQ-CQSZACIVSA-N

Drug Info: DrugBank

DrugBank ID	DB12597
Name	Asciminib
Groups	approved investigational
Description	Asciminib is a tyrosine kinase inhibitor (TKI) used in the treatment of chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). More specifically, it is an inhibitor of the ABL1 kinase activity of the BCR-ABL1 fusion protein[L38995] which serves as a driver of CML proliferation in most patients with the disease.[L39005] It has also shown benefit in Ph+ CML with the T315I mutation, which produces a mutant BCR-ABL1 which is typically treatment-resistant as compared to wild-type BCR-ABL1. Existing inhibitors of ABL compete at the ATP binding sites of these proteins and can be classified into those that target the active conformation of the kinase domain ([dasatinib], [bosutinib]) and those that target the inactive kinase domain ([imatinib], [nilotinib], [ponatinib]).[A241065] Asciminib is unique in that it acts as an allosteric inhibitor, binding at the myristoyl pocket of the BCR-ABL1 protein and locking it into an inactive conformation.[L38995,A241055] Asciminib received FDA approval on October 29, 2021 (Scemblix, Novartis AG).[L39000]
Synonyms	Asciminib Asciminib hydrochloride
Brand Names	Scemblix
Indication	Asciminib is indicated for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase who have been previously treated with ≥2 tyrosine kinase inhibitors.[L38995,L43493] It is also indicated in the treatment of Ph+ CML in adult patients with the T315I mutation.[L38995]
Categories	Antineoplastic Agents Antineoplastic and Immunomodulating Agents Bcr-Abl Tyrosine Kinase Inhibitors BCRP/ABCG2 Inhibitors BCRP/ABCG2 Substrates Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2C19 inhibitors (strength unknown) Cytochrome P-450 CYP2C19 Substrates Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 CYP2C9 Inhibitors (strength unknown) Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Inhibitors Cytochrome P-450 CYP3A4 Inhibitors (strength unknown) Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Substrates Enzyme Inhibitors Nicotinic Acids OATP1B1/SLCO1B1 Inhibitors OATP1B3 inhibitors OCT1 inhibitors P-glycoprotein inhibitors P-glycoprotein substrates Protein Kinase Inhibitors Pyridines Tyrosine Kinase Inhibitors UGT1A1 Inhibitors UGT2B17 substrates UGT2B7 substrates
ATC-Code	L01EA06
CAS number	1492952-76-7

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Tyrosine-protein kinase ABL1	MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNS...	unknown	inhibitor,allosteric modulator
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate,inhibitor
UDP-glucuronosyltransferase 2B7	MSVKWTSVILLIQLSFCFSSGNCGKVLVWAAEYSHWMNIKTILDELIQRG...	unknown	substrate
UDP-glucuronosyltransferase 2B17	MSLKWMSVFLLMQLSCYFSSGSCGKVLVWPTEYSHWINMKTILEELVQRG...	unknown	substrate
UDP-glucuronosyltransferase 1-1	MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQL...	unknown	inhibitor
Cytochrome P450 2C19	MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDV...	unknown	inhibitor
Cytochrome P450 2C9	MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDI...	unknown	inhibitor
ATP-binding cassette sub-family G member 2	MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKS...	unknown	substrate,inhibitor
P-glycoprotein 1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	unknown	substrate,inhibitor
Solute carrier organic anion transporter family member 1B1	MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKS...	unknown	inhibitor
Solute carrier organic anion transporter family member 1B3	MDQHQHLNKTAESASSEKKKTRRCNGFKMFLAALSFSYIAKALGGIIMKI...	unknown	inhibitor
Solute carrier family 22 member 1	MPTVDDILEQVGESGWFQKQAFLILCLLSAAFAPICVGIVFLGFTPDHHC...	unknown	inhibitor
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Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682