Drug Details
General Information of the Drug (ID: DR4199) | ||||
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Name |
Alpelisib
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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
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Disease | Breast cancer [ICD-11: 2C60] | Approved | [1] | |
Structure |
Click to Download Mol2D MOL |
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Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
Formula |
C19H22F3N5O2S
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PubChem CID | ||||
Canonical SMILES |
CC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F
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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
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InChIKey |
STUWGJZDJHPWGZ-LBPRGKRZSA-N
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CAS Number |
CAS 1217486-61-7
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ChEBI ID | ||||
TTD Drug ID | ||||
DrugBank ID |
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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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
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Up-regulation | Cleavage | CASP7 | Molecule Info |
Pathway MAP
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Up-regulation | Expression | H2AFX | Molecule Info |
Pathway MAP
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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 | ||||
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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 |