SELETALISIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H14ClF3N6O
Molecular Weight	482.845
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[O-][N+]1=CC=CC(=C1)C2=NC3=C(C=CC=C3Cl)C=C2[C@@H](NC4=NC=NC5=C4N=CC=C5)C(F)(F)F

InChI

InChIKey=LNLJHGXOFYUARS-OAQYLSRUSA-N

InChI=1S/C23H14ClF3N6O/c24-16-6-1-4-13-10-15(18(31-19(13)16)14-5-3-9-33(34)11-14)21(23(25,26)27)32-22-20-17(29-12-30-22)7-2-8-28-20/h1-12,21H,(H,29,30,32)/t21-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28442583 | https://www.ncbi.nlm.nih.gov/pubmed/28160012 | http://adisinsight.springer.com/drugs/800039987 | https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-005541-30/DE

Seletalisib (UCB-5857) is a potent, ATP-competitive, and selective phosphoinositide 3-kinase (PI3K) delta inhibitor. Findings from cellular assays of adaptive immunity demonstrated that seletalisib blocks human T-cell production of several cytokines from activated T-cells. Additionally, seletalisib inhibited B-cell proliferation and cytokine release. In human whole blood assays, seletalisib inhibited CD69 expression upon B-cell activation and anti-IgE-mediated basophil degranulation. Seletalisib safety, tolerability and pharmacokinetic/pharmacodynamic profiles support its continued clinical development in immune-inflammatory diseases. UCB Pharma is developing Seletalisib for the treatment of immune and inflammatory diseases including Activated PI3K delta Syndrome (APDS), Sjogren's syndrome and psoriasis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28442583	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Activated PI3K delta syndrome 1 Sources: https://www.ucb.com/our-science/Our-clinical-studies/UCB5857	Primary	Phase III 656	Unknown Approved Use Unknown
Sjogren's syndrome 8 Sources: http://adisinsight.springer.com/drugs/800039987	Primary	Phase II 1132	Unknown Approved Use Unknown
Psoriasis 84 Sources: http://adisinsight.springer.com/drugs/800039987	Primary	Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 MATE1 135 MATE2-K 2 OAT1 326 OAT3 339 BCRP 561 OATP1B1 406 BSEP 52 MRP2 205 OATP1B3 350 OCT1 327 OCT2 355

Drug as victim

Target	Modality	Activity
BSEP 52	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
MATE1 135	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
MATE2-K 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	yes [Km 19.7 uM]
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31678424/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01EOR7	https://www.1pchem.com/search?query=1P01EOR7
AbovChem LLC	HY-16754
Chem Scene	CS-6470	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-6470
Hairui	SEXF014	http://www.hairuichem.com/en/product/search.do?q=SEXF014
MedChem Express	HY-16754	https://www.medchemexpress.com/search.html?q=HY-16754&ft=&fa=&fp=
MolPort	MolPort-046-417-160	https://www.molport.com/shop/molecule-link/MolPort-046-417-160
Molnova	M11495	https://www.molnova.com/en/serch-list.html?keywords=M11495
Selleck Chemicals	S8560	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8560
ShangHai Biochempartner	BCP29404	http://www.biochempartner.com/search_BCP29404
eMolecules	227979306	https://orderbb.emolecules.com/search/#?query=227979306
eMolecules	275100301	https://orderbb.emolecules.com/search/#?query=275100301
eMolecules	303941050	https://orderbb.emolecules.com/search/#?query=303941050

PubMed

Title	Date	PubMed
A Dual-Administration Microtracer Technique to Characterize the Absorption, Distribution, Metabolism, and Excretion of [(14) C]Seletalisib (UCB5857) in Healthy Subjects.	2017 Dec	28650526
Seletalisib: Characterization of a Novel, Potent, and Selective Inhibitor of PI3Kδ.	2017 Jun	28442583
First-in-human studies of seletalisib, an orally bioavailable small-molecule PI3Kδ inhibitor for the treatment of immune and inflammatory diseases.	2017 May	28160012

Sample Use Guides

In Vivo Use Guide

The phase I, randomised, double-blind, placebo-controlled, single-centre studies (NCT02303509, NCT02207595) evaluated single and multiple oral doses of seletalisib (5-90 mg QD and 30 mg BID) in healthy adults and subjects with mild-to-moderate psoriasis (Study-1). Seletalisib was well tolerated at doses ≤15 mg (Study-1) and ≤45 mg QD (Study-2) for 14 days. No safety concerns or dose-limiting toxicities were identified (Study-1).

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

SELETALISIB

Official Name

English

N-((R)-1-(8-CHLORO-2-(1-OXOPYRIDIN-3-YL)QUINOLIN-3-YL)-2,2,2-TRIFLUOROETHYL)PYRIDO(3,2-D)PYRIMIDIN-4-YLAMINE

Systematic Name

English

seletalisib [INN]

Common Name

English

Seletalisib [WHO-DD]

Common Name

English

UCB-5857

Code

English

3-(8-CHLORO-3-((1R)-1-((PYRIDO(3,2-D)PYRIMIDIN-4-YL)AMINO)-2,2,2-TRIFLUOROETHYL)QUINOLIN-2-YL)PYRIDINE N-OXIDE

Systematic Name

English

UCB5857

Code

English

PYRIDO(3,2-D)PYRIMIDIN-4-AMINE, N-((1R)-1-(8-CHLORO-2-(1-OXIDO-3-PYRIDINYL)-3-QUINOLINYL)-2,2,2-TRIFLUOROETHYL)-

Systematic Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/18/1986