1LT

(2S)-N~1~-{4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl}pyrrolidine-1,2-dicarboxamide

Created:	2013-03-22
Last modified:	2022-09-30

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8 entries where 1LT is found as a standalone ligand1 entries where 1LT is covalently linked to polymer or other heterogen groups

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Chemical Details
Formal Charge	0
Atom Count	52
Chiral Atom Count	1
Bond Count	54
Aromatic Bond Count	11

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Chemical Component Summary
Name	(2S)-N~1~-{4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl}pyrrolidine-1,2-dicarboxamide
Synonyms	Alpelisib
Systematic Name (OpenEye OEToolkits)	(2S)-N1-[4-methyl-5-[2-[1,1,1-tris(fluoranyl)-2-methyl-propan-2-yl]pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
Formula	C₁₉ H₂₂ F₃ N₅ O₂ S
Molecular Weight	441.47
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	ACDLabs	12.01	O=C(Nc1nc(c(s1)c2ccnc(c2)C(C)(C)C(F)(F)F)C)N3C(C(=O)N)CCC3
SMILES	CACTVS	3.370	Cc1nc(NC(=O)N2CCC[CH]2C(N)=O)sc1c3ccnc(c3)C(C)(C)C(F)(F)F
SMILES	OpenEye OEToolkits	1.7.6	Cc1c(sc(n1)NC(=O)N2CCCC2C(=O)N)c3ccnc(c3)C(C)(C)C(F)(F)F
Canonical SMILES	CACTVS	3.370	Cc1nc(NC(=O)N2CCC[C@H]2C(N)=O)sc1c3ccnc(c3)C(C)(C)C(F)(F)F
Canonical SMILES	OpenEye OEToolkits	1.7.6	Cc1c(sc(n1)NC(=O)N2CCC[C@H]2C(=O)N)c3ccnc(c3)C(C)(C)C(F)(F)F
InChI	InChI	1.03	InChI=1S/C19H22F3N5O2S/c1-10-14(11-6-7-24-13(9-11)18(2,3)19(20,21)22)30-16(25-10)26-17(29)27-8-4-5-12(27)15(23)28/h6-7,9,12H,4-5,8H2,1-3H3,(H2,23,28)(H,25,26,29)/t12-/m0/s1
InChIKey	InChI	1.03	STUWGJZDJHPWGZ-LBPRGKRZSA-N

Drug Info: DrugBank

DrugBank ID	DB12015
Name	Alpelisib
Groups	approved investigational
Description	Alpelisib is a phosphatidylinositol 3-kinase (PI3K) inhibitor with potent antitumor activity. It works by selectively inhibiting class I PI3K p110α [A179203], which is the catalytic subunit of PI3K, a lipid kinase that plays a role in various biological processes, including proliferation, survival, differentiation, and metabolism. Alpelisib was designed to target this enzyme that appears to be mutated at a rate of nearly 30% in human cancers, leading to hyperactivation.[A179209] There are several isoform-specific PI3K inhibitors that are under clinical development or currently approved, such as [idelalisib] used for chronic lymphocytic leukemia (CLL).[A179209] Approved by the FDA in May 2019, alpelisib is the first approved PI3K inhibitor indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer in combination with [fulvestrant] for postmenopausal women and male patients. To initiate alpelisib therapy, it is required that the presence of a PIK3CA mutation in the tissue and/or liquid biopsy sample collection should be confirmed via FDA-approved diagnostic tests. Alpelisib is marketed under the trade name Piqray and is available as oral tablets. Studies evaluating the therapeutic effectiveness of alpelisib in other cancers, such as ovarian cancer [A179200] and colorectal cancer [A179203], are under ongoing investigations. Alpelisib was granted FDA approval on 24 May 2019.[L6652] In April 2022, the FDA granted the use of alpelisib in the treatment of PIK3CA-Related Overgrowth Spectrum (PROS) in adults and children who require systemic therapy.[L41384]
Synonyms	Alpelisib
Brand Names	Vijoice Piqray
Indication	Alpelisib is indicated in combination with fulvestrant to treat postmenopausal women, and men, with advanced or metastatic breast cancer. This cancer must be hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and PIK3CA mutated. The cancer must be detected by an FDA-approved test following progression on or after an endocrine-based regimen.[L6652] Alpelisib is also used to treat adult and pediatric patients two years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).[L41384]
Categories	Antineoplastic Agents Antineoplastic and Immunomodulating Agents BCRP/ABCG2 Inhibitors BCRP/ABCG2 Substrates Breast Neoplasms Class I Phosphatidylinositol 3-Kinases, antagonists & inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 CYP2B6 Inducers (moderate) Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2C19 inhibitors (strength unknown) Cytochrome P-450 CYP2C8 Inhibitors Cytochrome P-450 CYP2C8 Inhibitors (strength unknown) Cytochrome P-450 CYP2C9 Inducers Cytochrome P-450 CYP2C9 Inducers (moderate) Cytochrome P-450 CYP2C9 Inducers (strength unknown) Cytochrome P-450 CYP3A Inducers Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Inducers Cytochrome P-450 CYP3A4 Inducers (weak) Cytochrome P-450 CYP3A4 Inhibitors Cytochrome P-450 CYP3A4 Inhibitors (weak) Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A4 Substrates (strength unknown) Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index Cytochrome P-450 Enzyme Inducers Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Substrates Kinase Inhibitor Narrow Therapeutic Index Drugs P-glycoprotein inhibitors Phosphatidylinositol 3-Kinases, antagonists & inhibitors Phosphatidylinositol-3-kinase (Pi3K) inhibitors Protein Kinase Inhibitors Sulfur Compounds
ATC-Code	L01EM03
CAS number	1217486-61-7

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELF...	unknown	inhibitor
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate
Cytochrome P450 2C9	MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDI...	unknown	inducer
Cytochrome P450 2C8	MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDI...	unknown	inhibitor
Cytochrome P450 2C19	MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDV...	unknown	inhibitor
ATP-binding cassette sub-family G member 2	MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKS...	unknown	substrate
P-glycoprotein 1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	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