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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H22N6O
Molecular Weight 374.439
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GLASDEGIB

SMILES

CN1CC[C@H](C[C@@H]1C2=NC3=C(N2)C=CC=C3)NC(=O)NC4=CC=C(C=C4)C#N

InChI

InChIKey=SFNSLLSYNZWZQG-VQIMIIECSA-N
InChI=1S/C21H22N6O/c1-27-11-10-16(24-21(28)23-15-8-6-14(13-22)7-9-15)12-19(27)20-25-17-4-2-3-5-18(17)26-20/h2-9,16,19H,10-12H2,1H3,(H,25,26)(H2,23,24,28)/t16-,19-/m1/s1

HIDE SMILES / InChI

Description

PF-04449913 is a potent and selective inhibitor of the Hh signaling pathway through binding to the target, smoothened. PF-04449913 inhibits Hh signaling in vitro and has demonstrated significant antitumor activity in vivo. In the clinic, PF-04449913 is being evaluated both in hematological and solid malignancies, with a phase II trial currently underway in both fit and unfit patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Treatment-related adverse-events were nausea, dizziness, somnolence, QT prolongation and pruritus. Based on pre-clinical assessments, CYP3A4 is believed to be primarily involved in the metabolism of PF-04449913 that is why PF-04449913 plasma exposures and peak concentrations were increased following concurrent administration of ketoconazole (CYP3A4 inhibitor).

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

In Vivo Use Guide
100 mg daily in 4-week cycles for a total of 4 cycles. Dose escalation to 200 mg will be provided for patients who do not have at least hematologic improvement following 2 cycles, and dose reduction to 50 mg will be permitted for patients with significant toxicity.
Route of Administration: Oral
In Vitro Use Guide
Incubation of primary AML cells with PF‐913 (1 or 5 uM) attenuated Smoothened‐targeting gene transcripts that were activated by the addition of sonic hedgehog, and reduced the fraction of CD34+CD38− cells.
Name Type Language
GLASDEGIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
UREA, N-((2R,4R)-2-(1H-BENZIMIDAZOL-2-YL)-1-METHYL-4-PIPERIDINYL)-N'-(4-CYANOPHENYL)-
Systematic Name English
GLASDEGIB [INN]
Common Name English
GLASDEGIB [USAN]
Common Name English
N-((2R,4R)-2-(1H-BENZIMIDAZOL-2-YL)-1-METHYLPIPERIDIN-4-YL)-N'-(4-CYANOPHENYL)UREA
Systematic Name English
GLASDEGIB [WHO-DD]
Common Name English
PF-04449913
Code English
PF-4449913
Code English
Code System Code Type Description
ChEMBL
CHEMBL2043437
Created by admin on Tue Mar 06 10:37:42 UTC 2018 , Edited by admin on Tue Mar 06 10:37:42 UTC 2018
PRIMARY
EVMPD
SUB179278
Created by admin on Tue Mar 06 10:37:42 UTC 2018 , Edited by admin on Tue Mar 06 10:37:42 UTC 2018
PRIMARY
INN
9930
Created by admin on Tue Mar 06 10:37:42 UTC 2018 , Edited by admin on Tue Mar 06 10:37:42 UTC 2018
PRIMARY
PUBCHEM
25166913
Created by admin on Tue Mar 06 10:37:42 UTC 2018 , Edited by admin on Tue Mar 06 10:37:42 UTC 2018
PRIMARY SWITZERF
WIKIPEDIA
Glasdegib
Created by admin on Tue Mar 06 10:37:42 UTC 2018 , Edited by admin on Tue Mar 06 10:37:42 UTC 2018
PRIMARY
CAS
1095173-27-5
Created by admin on Tue Mar 06 10:37:42 UTC 2018 , Edited by admin on Tue Mar 06 10:37:42 UTC 2018
PRIMARY