ABROCITINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H21N5O2S
Molecular Weight	323.414
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCS(=O)(=O)N[C@H]1C[C@H](C1)N(C)C2=NC=NC3=C2C=CN3

InChI

InChIKey=IUEWXNHSKRWHDY-PHIMTYICSA-N

InChI=1S/C14H21N5O2S/c1-3-6-22(20,21)18-10-7-11(8-10)19(2)14-12-4-5-15-13(12)16-9-17-14/h4-5,9-11,18H,3,6-8H2,1-2H3,(H,15,16,17)/t10-,11+

HIDE SMILES / InChI

Molecular Formula	C14H21N5O2S
Molecular Weight	323.414
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27774822
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02201524 | https://www.google.com/patents/WO2014128591A1 | https://clinicaltrials.gov/ct2/show/NCT02780167

PF-04965842 is an orally administered selective Janus kinase 1 (JAK1) inhibitor. PF-04965842 is currently in clinical trials for the treatment of autoimmune diseases.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase JAK1 38 Target ID: CHEMBL2835 Sources: https://clinicaltrials.gov/ct2/show/NCT01835197	Inhibitor 8297	29.0 nM [IC50]
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27774822	Inhibitor 8297	803.0 nM [IC50]
Tyrosine-protein kinase TYK2 16 Target ID: CHEMBL3553 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27774822	Inhibitor 8297	1259.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Plaque psoriasis 16 Sources: https://clinicaltrials.gov/ct2/show/NCT02201524	Primary		Phase II 1132	Unknown Approved Use Unknown
Atopic dermatitis 43 Sources: https://clinicaltrials.gov/ct2/show/NCT02780167	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3334 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29672897	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-04965842 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3712 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29672897	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04965842 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
18230 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29672897	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-04965842 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
23740 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29672897	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04965842 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29672897	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-04965842 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.88 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29672897	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04965842 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270 Human hepatocytes 2 CYP2B6 664 CYP2C19 991

Drug as victim

Target	Modality	Activity
Human hepatocytes 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29298069/
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33749838/ \| https://cdn.ymaws.com/www.issx.org/resource/resmgr/past_meetings/12th_international_meeting/issx2019_abstract_book_onlin.pdf#page=140	major
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33749838/ \| https://cdn.ymaws.com/www.issx.org/resource/resmgr/past_meetings/12th_international_meeting/issx2019_abstract_book_onlin.pdf#page=140	major
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33749838/ \| https://cdn.ymaws.com/www.issx.org/resource/resmgr/past_meetings/12th_international_meeting/issx2019_abstract_book_onlin.pdf#page=140	minor
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33749838/ \| https://cdn.ymaws.com/www.issx.org/resource/resmgr/past_meetings/12th_international_meeting/issx2019_abstract_book_onlin.pdf#page=140	minor
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29298069/	yes

Sourcing

Vendor/Aggregator	ID	URL
Molnova	M12393	https://www.molnova.com/en/serch-list.html?keywords=M12393
MuseChem	I011983	https://www.musechem.com/product/I011983.html
Selleck Chemicals	S8765	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8765

PubMed

Title	Date	PubMed
Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2.	2017 Feb	27774822

Patents

Sample Use Guides

In Vivo Use Guide

200 mg daily, 400 mg daily and 200 mg twice daily for 4 weeks

Route of Administration: Oral

In Vitro Use Guide

Canine whole blood was collected in sodium heparin tubes from 29 beagle dogs and 23 mixed breed dogs. Whole blood (20 μL) was plated in 96-well plates (Costar 3598) with 180 μL of medium (RPMI 1640, Gibco #21870-076, with 1% heat inactivated fetal bovine serum, Gibco #10082-39, 292 μg/ml L-glutamine, Gibco #250030-081, 100 u/ml penicillin and 100μg streptomycin per ml, Gi bco #15 140- 122) containing vehicle control or test compound (0.001 to 10 μΜ), concanavalin A (ConA; 1 μg/ml, Sigma C5275), and canine inter-leukin-2 (IL-2 ; 50 ng/ml , R&D Systems 1815-CL/CF). Wells containing whole blood, medium with vehicle control and no ConA or I L-2 were used as background controls. Plates were incubated at 37° C for 48 hours. Tritiated thymidine, 0.4 μα/well (Perkin Elmer, Net027A-005 MC), was added for 20 additional hours. Plates were frozen and then thawed, washed and filtered using a Brandel MLR-96 cell harvester and pre-wet filter mats (Wallac 1205-401, Perkin Elmer). Filters were d ried at 60° C for one hour (Precision 16EG convection oven) and placed into filter sample bags (Wallac 1205-411, Perkin Elmer) with 10 mL of scintillant (Wallac 1205-440, Perkin Elmer). Sealed filters were counted on a LKB Wallac 1205 Betaplate liquid scintillation counter.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:58:58 UTC 2023` Edited by `admin` on `Sat Dec 16 08:58:58 UTC 2023`
Record UNII	73SM5SF3OR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ABROCITINIB

Official Name

English

PF-04965842

Code

English

CIBINQO

Brand Name

English

N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide

Systematic Name

English

ABROCITINIB [JAN]

Common Name

English

1-PROPANESULFONAMIDE, N-(CIS-3-(METHYL-7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)CYCLOBUTYL)-

Systematic Name

English

abrocitinib [INN]

Common Name

English

N-((1S,3S)-3-(METHYL(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)AMINO)CYCLOBUTYL)PROPANE-1-SULFONAMIDE

Systematic Name

English

ABROCITINIB [USAN]

Common Name

English

N-(3-(METHYL(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)AMINO)CYCLOBUTYL)PROPANE-1-SULFONAMIDE, CIS-

Systematic Name

English

Abrocitinib [WHO-DD]

Common Name

English

Code System Code Type Description

ChEMBL

CHEMBL3544929