Drug Details

General Information of the Drug (ID: DR4199)
Name
Alpelisib
Synonyms
alpelisib; 1217486-61-7; BYL-719; BYL719; NVP-BYL719; Piqray; 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; UNII-08W5N2C97Q; BYL 719; (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide; CHEMBL2396661; 08W5N2C97Q; C19H22F3N5O2S; (2S)-1-N-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide; (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; (S)-N1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide.; 1,2-Pyrrolidinedicarboxamide, N1-(4-methyl-5-(2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl)-2-thiazolyl)-, (2S)-; 1,2-PYRROLIDINEDICARBOXAMIDE, N1-[4-METHYL-5-[2-(2,2,2-TRIFLUORO-1,1-DIMETHYLETHYL)-4-PYRIDINYL]-2-THIAZOLYL]-, (2S)-; 4jps; Piqray (TN); Alpelisib [USAN:INN]; QCR-1; Alpelisib (JAN/USAN/INN); cc-697; GTPL7955; SCHEMBL1911869; CHEBI:93752; DTXSID70153355; EX-A405; BYL 719; BYL719; AOB87192; NVP-BYL719 (BYL719); 2294AH; BDBM50436459; MFCD22417085; NSC765974; NSC800065; s2814; ZINC68198368; AKOS022186315; CCG-269139; CS-0663; DB12015; NSC-765974; NSC-800065; SB16575; NCGC00346717-03; NCGC00346717-06; (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidine; (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-(4-methyl-5-(2-(2,2,2-trifluoro-1,1-dimethylethyl)-pyridin-4-yl)thiazol-2-yl)amide; 1217486-47-9; AS-16349; HY-15244; AB0094905; SW220128-1; cas:1217486-61-7;BYL-719; D11011; W-5917; J-004627; Q27074391; 1LT; BYL-719; ; ; (2S)-1-N-[4-Methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
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Molecular Type
Small molecule
Disease Breast cancer [ICD-11: 2C60] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C19H22F3N5O2S
PubChem CID
56649450
Canonical SMILES
CC1=C(SC(=N1)NC(=O)N2CCCC2C(=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
CAS Number
CAS 1217486-61-7
ChEBI ID
CHEBI:93752
TTD Drug ID
D0W7HE
DrugBank ID
DB12015
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Paclitaxel      Taxus brevifolia     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
Up-regulation Expression H2AFX  Molecule Info 
Pathway MAP
                    In-vitro Model SNU-1 CVCL_0099 Gastric adenocarcinoma Homo sapiens
SNU-16 CVCL_0076 Gastric adenocarcinoma Homo sapiens
SNU-484 CVCL_0100 Gastric adenocarcinoma Homo sapiens
SNU-638 CVCL_0102 Gastric adenocarcinoma Homo sapiens
MKN1 CVCL_1415 Gastric adenosquamous carcinoma Homo sapiens
SNU-601 CVCL_0101 Gastric adenocarcinoma Homo sapiens
SNU-668 CVCL_5081 Gastric adenocarcinoma Homo sapiens
AGS CVCL_0139 Gastric adenocarcinoma Homo sapiens
                    In-vivo Model For a xenograft model, 1 * 107 MKN1 cells were implanted subcutaneously into both flanks of each Balb/c mouse.
                    Experimental
                    Result(s)		 Alpelisib alone or in combination with paclitaxel demonstrated promising anti-tumor activity in in vitro and in vivo models of PIK3CA-mutant GC via inactivating PI3K down-stream molecules, increasing DNA damage response, and apoptosis.
Target and Pathway
Target(s) Phosphatidylinositol-4-kinase alpha (PI4KA)  Molecule Info  [1]
PI3-kinase alpha (PIK3CA)  Molecule Info  [1]
BioCyc Superpathway of inositol phosphate compounds Click to Show/Hide
2 3-phosphoinositide biosynthesis
KEGG Pathway Inositol phosphate metabolism Click to Show/Hide
2 Metabolic pathways
3 Phosphatidylinositol signaling system
4 ErbB signaling pathway
5 Ras signaling pathway
6 Rap1 signaling pathway
7 cGMP-PKG signaling pathway
8 cAMP signaling pathway
9 Chemokine signaling pathway
10 HIF-1 signaling pathway
11 FoxO signaling pathway
12 Sphingolipid signaling pathway
13 mTOR signaling pathway
14 PI3K-Akt signaling pathway
15 AMPK signaling pathway
16 Apoptosis
17 Adrenergic signaling in cardiomyocytes
18 VEGF signaling pathway
19 Osteoclast differentiation
20 Focal adhesion
21 Signaling pathways regulating pluripotency of stem cells
22 Platelet activation
23 Toll-like receptor signaling pathway
24 Jak-STAT signaling pathway
25 Natural killer cell mediated cytotoxicity
26 T cell receptor signaling pathway
27 B cell receptor signaling pathway
28 Fc epsilon RI signaling pathway
29 Fc gamma R-mediated phagocytosis
30 TNF signaling pathway
31 Leukocyte transendothelial migration
32 Neurotrophin signaling pathway
33 Cholinergic synapse
34 Inflammatory mediator regulation of TRP channels
35 Regulation of actin cytoskeleton
36 Insulin signaling pathway
37 Progesterone-mediated oocyte maturation
38 Estrogen signaling pathway
39 Prolactin signaling pathway
40 Thyroid hormone signaling pathway
41 Oxytocin signaling pathway
42 Regulation of lipolysis in adipocytes
43 Type II diabetes mellitus
44 Non-alcoholic fatty liver disease (NAFLD)
45 Aldosterone-regulated sodium reabsorption
46 Carbohydrate digestion and absorption
47 Bacterial invasion of epithelial cells
48 Chagas disease (American trypanosomiasis)
49 Toxoplasmosis
50 Amoebiasis
51 Hepatitis C
52 Hepatitis B
53 Measles
54 Influenza A
55 HTLV-I infection
56 Epstein-Barr virus infection
57 Pathways in cancer
58 Viral carcinogenesis
59 Proteoglycans in cancer
60 MicroRNAs in cancer
61 Colorectal cancer
62 Renal cell carcinoma
63 Pancreatic cancer
64 Endometrial cancer
65 Glioma
66 Prostate cancer
67 Melanoma
68 Chronic myeloid leukemia
69 Acute myeloid leukemia
70 Small cell lung cancer
71 Non-small cell lung cancer
72 Central carbon metabolism in cancer
73 Choline metabolism in cancer
Panther Pathway Angiogenesis Click to Show/Hide
2 Apoptosis signaling pathway
3 Axon guidance mediated by netrin
4 B cell activation
5 EGF receptor signaling pathway
6 Endothelin signaling pathway
7 FGF signaling pathway
8 Hypoxia response via HIF activation
9 Inflammation mediated by chemokine and cytokine signaling pathway
10 Insulin/IGF pathway-protein kinase B signaling cascade
11 Integrin signalling pathway
12 Interleukin signaling pathway
13 PDGF signaling pathway
14 PI3 kinase pathway
15 T cell activation
16 VEGF signaling pathway
17 p53 pathway
18 Ras Pathway
19 p53 pathway feedback loops 2
Pathwhiz Pathway Inositol Metabolism Click to Show/Hide
2 Phosphatidylinositol Phosphate Metabolism
3 Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
4 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
5 Fc Epsilon Receptor I Signaling in Mast Cells
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells Click to Show/Hide
2 BCR signaling pathway
3 ErbB4 signaling events
4 Insulin Pathway
5 GMCSF-mediated signaling events
6 Atypical NF-kappaB pathway
7 IL4-mediated signaling events
8 Plasma membrane estrogen receptor signaling
9 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
10 Signaling events mediated by PTP1B
11 EPHB forward signaling
12 Osteopontin-mediated events
13 Reelin signaling pathway
14 Nectin adhesion pathway
15 TRAIL signaling pathway
16 CDC42 signaling events
17 Signaling events regulated by Ret tyrosine kinase
18 Signaling events mediated by TCPTP
19 Angiopoietin receptor Tie2-mediated signaling
20 FAS (CD95) signaling pathway
21 SHP2 signaling
22 Netrin-mediated signaling events
23 IL1-mediated signaling events
24 IL2-mediated signaling events
25 CXCR4-mediated signaling events
26 IGF1 pathway
27 EGF receptor (ErbB1) signaling pathway
28 IL5-mediated signaling events
29 Class I PI3K signaling events
30 IL2 signaling events mediated by PI3K
31 p75(NTR)-mediated signaling
32 E-cadherin signaling in the nascent adherens junction
33 Integrins in angiogenesis
34 IFN-gamma pathway
35 ErbB1 downstream signaling
36 ErbB2/ErbB3 signaling events
37 IL3-mediated signaling events
38 IL6-mediated signaling events
39 E-cadherin signaling in keratinocytes
40 PDGFR-beta signaling pathway
41 Neurotrophic factor-mediated Trk receptor signaling
42 Nephrin/Neph1 signaling in the kidney podocyte
43 IL23-mediated signaling events
44 PDGFR-alpha signaling pathway
45 Signaling events mediated by the Hedgehog family
46 Nongenotropic Androgen signaling
47 Internalization of ErbB1
48 CXCR3-mediated signaling events
49 VEGFR1 specific signals
50 Signaling events mediated by Stem cell factor receptor (c-Kit)
51 IL2 signaling events mediated by STAT5
52 Signaling events mediated by VEGFR1 and VEGFR2
53 PAR1-mediated thrombin signaling events
54 a6b1 and a6b4 Integrin signaling
55 Ephrin B reverse signaling
56 N-cadherin signaling events
57 Trk receptor signaling mediated by PI3K and PLC-gamma
58 EPHA2 forward signaling
59 VEGFR3 signaling in lymphatic endothelium
60 FGF signaling pathway
61 Signaling events mediated by focal adhesion kinase
Reactome PI3K Cascade Click to Show/Hide
2 GPVI-mediated activation cascade
3 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
4 PI3K events in ERBB4 signaling
5 PIP3 activates AKT signaling
6 GAB1 signalosome
7 PI3K events in ERBB2 signaling
8 PI3K/AKT activation
9 Role of phospholipids in phagocytosis
10 Tie2 Signaling
11 Constitutive Signaling by Aberrant PI3K in Cancer
12 DAP12 signaling
13 Role of LAT2/NTAL/LAB on calcium mobilization
14 Nephrin interactions
15 Costimulation by the CD28 family
16 CD28 dependent PI3K/Akt signaling
17 G beta:gamma signalling through PI3Kgamma
18 G alpha (q) signalling events
19 G alpha (12/13) signalling events
20 VEGFA-VEGFR2 Pathway
21 Interleukin-3, 5 and GM-CSF signaling
22 Constitutive Signaling by EGFRvIII
23 PI-3K cascade:FGFR1
24 PI-3K cascade:FGFR2
25 PI-3K cascade:FGFR3
26 PI-3K cascade:FGFR4
27 Interleukin receptor SHC signaling
28 Regulation of signaling by CBL
WikiPathways Toll-like receptor signaling pathway Click to Show/Hide
2 Serotonin HTR1 Group and FOS Pathway
3 DNA Damage Response (only ATM dependent)
4 G13 Signaling Pathway
5 Regulation of Actin Cytoskeleton
6 Insulin Signaling
7 IL-4 Signaling Pathway
8 Signaling of Hepatocyte Growth Factor Receptor
9 Transcriptional activation by NRF2
10 IL1 and megakaryotyces in obesity
11 Signaling by ERBB4
12 Signaling by ERBB2
13 Fc epsilon receptor (FCERI) signaling
14 PI Metabolism
15 Interleukin-2 signaling
16 Fcgamma receptor (FCGR) dependent phagocytosis
17 Signaling by SCF-KIT
18 DAP12 interactions
19 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
20 Gastrin-CREB signalling pathway via PKC and MAPK
21 PIP3 activates AKT signaling
22 Integrated Pancreatic Cancer Pathway
23 Prostate Cancer
24 Signaling Pathways in Glioblastoma
25 TSLP Signaling Pathway
26 Regulation of Microtubule Cytoskeleton
27 TSH signaling pathway
28 SREBP signalling
29 TCR signaling
30 Signaling by PDGF
31 Signaling by Insulin receptor
32 Signaling by FGFR
33 Signaling by EGFR
34 NGF signalling via TRKA from the plasma membrane
35 Nephrin interactions
36 Interleukin-3, 5 and GM-CSF signaling
37 GPVI-mediated activation cascade
38 GPCR downstream signaling
39 Costimulation by the CD28 family
40 Cell surface interactions at the vascular wall
41 MicroRNAs in cardiomyocyte hypertrophy
42 Angiogenesis
43 Regulation of toll-like receptor signaling pathway
44 AMPK Signaling
References
Reference 1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Reference 2 PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer. Sci Rep. 2020 Jul 23;10(1):12308.
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