Drug Information

Drug (ID: DG00284) and It's Reported Resistant Information

Name	Alpelisib
Synonyms	Alpelisib; 1217486-61-7; BYL-719; BYL719; UNII-08W5N2C97Q; BYL 719; Alpelisib (BYL719); (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide; NVP-BYL719; (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide; CHEMBL2396661; 08W5N2C97Q; AK146107; C19H22F3N5O2S; (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)-pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide Click to Show/Hide
Indication	In total 2 Indication(s) Breast cancer [ICD-11: 2C60] Approved [1], [2] Solid tumour/cancer [ICD-11: 2A00-2F9Z] Phase 2 [1], [2]
Structure
Drug Resistance Disease(s)	Disease(s) with Clinically Reported Resistance for This Drug (1 diseases) Breast cancer [ICD-11: 2C60] [1], [2]
Target	PI3-kinase alpha (PIK3CA)	PK3CA_HUMAN	[2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	C19H22F3N5O2S
IsoSMILES	CC1=C(SC(=N1)NC(=O)N2CCC[C@H]2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F
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	STUWGJZDJHPWGZ-LBPRGKRZSA-N
PubChem CID	56649450
ChEBI ID	CHEBI:93752
TTD Drug ID	D0W7HE
INTEDE ID	DR0074
DrugBank ID	DB12015

Type(s) of Resistant Mechanism of This Drug

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Click to Show/Hide the Resistance Disease of This Class

Breast cancer [ICD-11: 2C60]

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: Phosphatase and tensin homolog (PTEN)			[1], [2]
Molecule Alteration	Structural variation	Copy number loss	Molecule Info
Resistant Disease	Breast cancer [ICD-11: 2C60.3]		Disease Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K signaling pathway	Activation	hsa04151
Experiment for Molecule Alteration	Whole genome sequencing assay; Whole exome sequencing assay
Experiment for Drug Resistance	Tetrazolium-based MTT assay
Mechanism Description	We conclude that parallel genetic evolution of separate metastatic sites with different PTEN genomic alterations leads to a convergent PTEN-null phenotype resistant to PI(3)kalpha inhibition.

References

Ref 1	Convergent loss of PTEN leads to clinical resistance to a PI(3)KAlpha inhibitor. Nature. 2015 Feb 12;518(7538):240-4. doi: 10.1038/nature13948. Epub 2014 Nov 17.
Ref 2	Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun. 2016 Jun 10;7:11815. doi: 10.1038/ncomms11815.