SERABELISIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17N5O3
Molecular Weight	363.37
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=CC(=CC=C2O1)C3=CN4C(=CN=C4C=C3)C(=O)N5CCOCC5

InChI

InChIKey=BLGWHBSBBJNKJO-UHFFFAOYSA-N

InChI=1S/C19H17N5O3/c20-19-22-14-9-12(1-3-16(14)27-19)13-2-4-17-21-10-15(24(17)11-13)18(25)23-5-7-26-8-6-23/h1-4,9-11H,5-8H2,(H2,20,22)

HIDE SMILES / InChI

Molecular Formula	C19H17N5O3
Molecular Weight	363.37
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Serabelisib (INK1117 and TAK-117) is an orally bioavailable, PI3K p110α- isoform-specific inhibitor with an in vitro IC50 of 15 nM, highly selective against other isoforms (p110β, p110γ, and p110δ) and mTOR (no significant inhibitions at 1 μM concentration). It displayed significant efficacy in several PI3Kα mutant-specific preclinical mouse xenograft tumor models, and blocked signaling to Akt and inhibited the growth of cancer cells harboring wild-type or mutated p110α. Preclinical studies showed TAK-117 to have the low potential for disrupting glucose metabolism or for causing cardiac adverse events; in rats and monkeys, doses up to 50 mg/kg/day were well tolerated. Serabelisib is currently under clinical evaluation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
PI3-kinase p110-delta subunit 37	Inhibitor 7468		13900.0 nM [IC50]
PI3-kinase p110-gamma subunit 28	Inhibitor 7468		1900.0 nM [IC50]
PI3-kinase p110-beta subunit 27	Inhibitor 7468		4500.0 nM [IC50]
PI3-kinase p110-alpha subunit 32	Inhibitor 7468	Neoplasms	15.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase
Renal Cell Carcinoma 22	Primary	PI3-kinase p110-alpha subunit	Phase II 1079
Non-Small Cell Lung Cancer 78	Primary	PI3-kinase p110-alpha subunit	Phase II 1079
Neoplasms 249	Primary	PI3-kinase p110-alpha subunit	Phase II 1079

PubMed

Title	Date	PubMed
A First-in-Human, Phase I, Dose-Escalation Study of TAK-117, a Selective PI3Kα Isoform Inhibitor, in Patients with Advanced Solid Malignancies.	2017 Sep 1	28490463

Patents

Sample Use Guides

In Vivo Use Guide

In total, 24 patients were assigned to once-daily (6 at 100 mg, 6 at 150 mg, 8 at 200 mg, and 4 at 300 mg), 27 to Monday–Wednesday–Friday (MWF) (3 patients each at 200, 300, 400, and 600 mg, 12 at 900 mg, and 3 at 1,200 mg), and 20 to MTuW (3 patients each at 200, 400, and 600 mg, and 11 patients at 900 mg) dosing.

Route of Administration: Oral

In Vitro Use Guide

SK-OV-3 and U87MG cell lines were obtained from ATCC. A total of 5000 cells/well in low serum media (0.2% FBS) were seeded in triplicate wells of a 96-well flat bottom culture plate for 18 h to adhere. Media was aspirated and inhibitors in 0.2% FBS media were added to each well at the indicated concentrations. After 48 h, cell viability was determined using the MTS assay (Cell Titer 96 Aqueous One solution cell proliferation assay kit; Promega) with absorbance (490 nm) measured in a microplate spectrophotometer.

Substance Class	Chemical Created by `admin` on `Mon Oct 21 22:43:56 UTC 2019` Edited by `admin` on `Mon Oct 21 22:43:56 UTC 2019`
Record UNII	43J9Q56T3W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SERABELISIB

Official Name

English

MLN-1117

Code

English

INK-1117

Code

English

SERABELISIB [INN]

Common Name

English

AGN-PC-0DB6FL

Code

English

METHANONE, (6-(2-AMINO-5-BENZOXAZOLYL)IMIDAZO(1,2-A)PYRIDIN-3-YL)-4-MORPHOLINYL-

Systematic Name

English

(6-(2-AMINO-5-BENZOXAZOLYL)IMIDAZO(1,2-A)PYRIDIN-3-YL)-4-MORPHOLINYLMETHANONE

Systematic Name

English

INK1117

Code

English

SERABELISIB [WHO-DD]

Common Name

English

MLN1117

Code

English

TAK-117

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825