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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
Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
2012 Feb 9
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