Sapanisertib Explained

Iupac Name:	5-(4-Amino-1-propan-2-ylpyrazolo[3,4-''d'']pyrimidin-3-yl)-1,3-benzoxazol-2-amine
Cas Number:	1224844-38-5
Unii:	JGH0DF1U03
Pubchem:	45375953
Chebi:	91450
Kegg:	D11183
C:	15
H:	15
N:	7
O:	1
Stdinchi:	1S/C15H15N7O/c1-7(2)22-14-11(13(16)18-6-19-14)12(21-22)8-3-4-10-9(5-8)20-15(17)23-10/h3-7H,1-2H3,(H2,17,20)(H2,16,18,19)
Stdinchikey:	GYLDXIAOMVERTK-UHFFFAOYSA-N
Smiles:	CC(C)N1C2=C(C(=N1)C3=CC4=C(C=C3)OC(=N4)N)C(=NC=N2)N

Sapanisertib (also known as MLN0128, INK128 and TAK-228) is an experimental small molecule inhibitor of mTOR which is administered orally. It targets both mTORC1 and mTORC2.^[1]

Developed by Millennium Pharmaceuticals,^{[2] [3] [4]} and is in phase II clinical trials for breast cancer, endometrial cancer, glioblastoma, renal cell carcinoma, and thyroid cancer.^[5] The drug has been well tolerated by patients with advanced solid tumours in Phase I trials.^[6]

Notes and References

1. Panchal II, Badeliya SN, Patel R, Patel A, Devaligar A . In silico Analysis and Molecular Docking Studies of Novel 4-Amino-3- (Isoquinolin-4-yl)-1H-Pyrazolo[3,4-d]Pyrimidine Derivatives as Dual PI3-K/mTOR Inhibitors . Current Drug Discovery Technologies . 2019 . 16 . 3 . 297–306 . 30387396 . 10.2174/1568009618666181102144934 . 54344624 .
2. Guo N, Azadniv M, Coppage M, Nemer M, Mendler J, Becker M, Liesveld J . Effects of Neddylation and mTOR Inhibition in Acute Myelogenous Leukemia . Translational Oncology . 12 . 4 . 602–613 . April 2019 . 30699367 . 10.1016/j.tranon.2019.01.001 . 6348338 .
3. Ouvry G, Clary L, Tomas L, Aurelly M, Bonnary L, Borde E, Bouix-Peter C, Chantalat L, Defoin-Platel C, Deret S, Forissier M, Harris CS, Isabet T, Lamy L, Luzy AP, Pascau J, Soulet C, Taddei A, Taquet N, Thoreau E, Varvier E, Vial E, Hennequin LF . 6 . Impact of Minor Structural Modifications on Properties of a Series of mTOR Inhibitors . ACS Medicinal Chemistry Letters . 10 . 11 . 1561–1567 . November 2019 . 31749911 . 10.1021/acsmedchemlett.9b00401 . 6862343 .
4. Arnold A, Yuan M, Price A, Harris L, Eberhart CG, Raabe EH . Synergistic activity of mTORC1/2 kinase and MEK inhibitors suppresses pediatric low-grade glioma tumorigenicity and vascularity . Neuro-Oncology . 22 . 4 . 563–574 . April 2020 . 31841591 . 10.1093/neuonc/noz230 . 7158655 .
5. Web site: Sapanisertib - Takeda Oncology . Adis Insight . Springer Nature Switzerland AG .
6. Moore KN, Bauer TM, Falchook GS, Chowdhury S, Patel C, Neuwirth R, Enke A, Zohren F, Patel MR . 6 . Phase I study of the investigational oral mTORC1/2 inhibitor sapanisertib (TAK-228): tolerability and food effects of a milled formulation in patients with advanced solid tumours . ESMO Open . 3 . 2 . e000291 . February 2018 . 29464110 . 10.1136/esmoopen-2017-000291 . 5812400 . free .