U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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=CC=CC=C3N2)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
Molecular Formula C21H22N6O
Molecular Weight 374.439
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800030686 | http://www.pharmacodia.com/yaodu/html/v1/chemicals/86f3f50a6f945bbfa351e55faac043fb.html

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

Pfizer
420
Curator's Comment: # Pfizer

Approval Year

2018
436
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
DAURISMO

Approved Use

Daurismo is specifically indicated for use in combination with low-dose cytarabine for the treatment of newly-diagnosed acute myeloid leukemia in adult patients who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.

Launch Date

2018
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1252 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GLASDEGIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
17210 ng × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GLASDEGIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
17.4 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GLASDEGIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
9%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GLASDEGIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
640 mg 1 times / day steady, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: steady
Dose: 640 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 8
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
DLT: Fatigue, Dehydration...
Dose limiting toxicities:
Fatigue (grade 2, 1 patient)
Dehydration (grade 2-3, 2 patients)
Dizziness (grade 2, 1 patient)
Hypotension (grade 2, 1 patient)
Nausea (grade 3, 1 patient)
Vomiting (grade 3, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
320 mg 1 times / day steady, oral
MTD
Dose: 320 mg, 1 times / day
Route: oral
Route: steady
Dose: 320 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 7
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Disc. AE: Dehydration, Fatigue...
AEs leading to
discontinuation/dose reduction:
Dehydration (2 patients)
Fatigue (2 patients)
Nausea (2 patients)
Vomiting (2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
400 mg 1 times / day steady, oral
MTD
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
unhealthy, 69 years (range: 25–89 years)
n = 9
Health Status: unhealthy
Condition: myeloid malignancies
Age Group: 69 years (range: 25–89 years)
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
600 mg 1 times / day steady, oral
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
unhealthy, 69 years (range: 25–89 years)
n = 5
Health Status: unhealthy
Condition: myeloid malignancies
Age Group: 69 years (range: 25–89 years)
Sex: M+F
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
DLT: Peripheral oedema...
Disc. AE: Electrocardiogram QTc interval prolonged...
Dose limiting toxicities:
Peripheral oedema (grade 3, 20%)
AEs leading to
discontinuation/dose reduction:
Electrocardiogram QTc interval prolonged (grade 3, 4 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
80 mg 1 times / day steady, oral
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
unhealthy, 69 years (range: 25–89 years)
n = 8
Health Status: unhealthy
Condition: myeloid malignancies
Age Group: 69 years (range: 25–89 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
DLT: Hypoxia, Pleural effusion...
Dose limiting toxicities:
Hypoxia (grade 3, 17%)
Pleural effusion (grade 3, 17%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
100 mg 1 times / day multiple, oral
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
pregnant
Health Status: pregnant
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
Other AEs: Fetal damage...
Other AEs:
Fetal damage (grade 5)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Dizziness grade 2, 1 patient
DLT
640 mg 1 times / day steady, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: steady
Dose: 640 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 8
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Hypotension grade 2, 1 patient
DLT
640 mg 1 times / day steady, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: steady
Dose: 640 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 8
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Fatigue grade 2, 1 patient
DLT, Disc. AE
640 mg 1 times / day steady, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: steady
Dose: 640 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 8
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Dehydration grade 2-3, 2 patients
DLT, Disc. AE
640 mg 1 times / day steady, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: steady
Dose: 640 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 8
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Nausea grade 3, 1 patient
DLT, Disc. AE
640 mg 1 times / day steady, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: steady
Dose: 640 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 8
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Vomiting grade 3, 1 patient
DLT, Disc. AE
640 mg 1 times / day steady, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: steady
Dose: 640 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 8
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Dehydration 2 patients
Disc. AE
320 mg 1 times / day steady, oral
MTD
Dose: 320 mg, 1 times / day
Route: oral
Route: steady
Dose: 320 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 7
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Fatigue 2 patients
Disc. AE
320 mg 1 times / day steady, oral
MTD
Dose: 320 mg, 1 times / day
Route: oral
Route: steady
Dose: 320 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 7
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Nausea 2 patients
Disc. AE
320 mg 1 times / day steady, oral
MTD
Dose: 320 mg, 1 times / day
Route: oral
Route: steady
Dose: 320 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 7
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Vomiting 2 patients
Disc. AE
320 mg 1 times / day steady, oral
MTD
Dose: 320 mg, 1 times / day
Route: oral
Route: steady
Dose: 320 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
unhealthy, 61.0 years (range: 27–76 years)
n = 7
Health Status: unhealthy
Condition: Advanced Solid Tumors
Age Group: 61.0 years (range: 27–76 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/25388167
Peripheral oedema grade 3, 20%
DLT
600 mg 1 times / day steady, oral
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
unhealthy, 69 years (range: 25–89 years)
n = 5
Health Status: unhealthy
Condition: myeloid malignancies
Age Group: 69 years (range: 25–89 years)
Sex: M+F
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
Electrocardiogram QTc interval prolonged grade 3, 4 patients
Disc. AE
600 mg 1 times / day steady, oral
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
unhealthy, 69 years (range: 25–89 years)
n = 5
Health Status: unhealthy
Condition: myeloid malignancies
Age Group: 69 years (range: 25–89 years)
Sex: M+F
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
Hypoxia grade 3, 17%
DLT
80 mg 1 times / day steady, oral
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
unhealthy, 69 years (range: 25–89 years)
n = 8
Health Status: unhealthy
Condition: myeloid malignancies
Age Group: 69 years (range: 25–89 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
Pleural effusion grade 3, 17%
DLT
80 mg 1 times / day steady, oral
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
unhealthy, 69 years (range: 25–89 years)
n = 8
Health Status: unhealthy
Condition: myeloid malignancies
Age Group: 69 years (range: 25–89 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/26688487
Fetal damage grade 5
100 mg 1 times / day multiple, oral
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
pregnant
Health Status: pregnant
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210656s000lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1767
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2B6
810

CYP2C8
911

CYP2C19
1478

CYP3A
214

P-gp
1461

BCRP
699

MATE1
306

MATE2
263

OATP1B1
788

OATP1B3
706

OAT1
599

OAT3
642

OCT2
647

UGT1A4
77

UGT1A6
108

UGT2B7
146

UGT2B15
64

CYP1A
72

CYP2E1
882

UGT1A9
116
CYP3A
191

CYP2C8
693

UGT1A9
380

P-gp
1537

BCRP
561

OAT1
326

OAT3
339

OCT2
355

MATE1
135

MATE2
96

OATP1B1
406

OATP1B3
350
CYP1A2
701

CYP2B6
547

CYP3A
129
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OATP1B1
803
 no [IC50 26 uM]
OATP1B3
715
 no [IC50 26 uM]
CYP2D6
1891
 no [IC50 88 uM]
UGT1A4
80
 no [IC50 >131 uM]
UGT1A6
141
 no [IC50 >131 uM]
UGT2B15
64
 no [IC50 >131 uM]
UGT2B7
157
 no [IC50 >131 uM]
OAT1
603
 no [IC50 >50 uM]
OAT3
644
 no [IC50 >50 uM]
OCT2
648
 no [IC50 >50 uM]
CYP1A
121
 no [IC50 >94 uM]
CYP2B6
1001
 no [IC50 >94 uM]
CYP2C19
1553
 no [IC50 >94 uM]
CYP2C9
1819
 no [IC50 >94 uM]
CYP3A
298
 no [IC50 >94 uM]
CYP1A2
1692
 no
CYP1A2
1692
 no
CYP2B6
1001
 no
CYP2C8
965
 no
CYP2E1
970
 no
CYP3A
298
 no
MATE2
263
 yes [IC50 1.2 uM]
BCRP
773
 yes [IC50 4.6 uM]
MATE1
308
 yes [IC50 4.9 uM]
P-gp
1650
 yes
UGT1A9
121
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
MATE1
135
 no
MATE2
96
 no
OAT1
326
 no
OAT3
339
 no
OATP1B1
406
 no
OATP1B3
350
 no
OCT2
355
 no
BCRP
561
 yes
CYP2C8
693
 yes
P-gp
1537
 yes
UGT1A9
380
 yes
CYP3A
191
 yes
yes (co-administration study)
Comment: Co-administration of ketoconazole (a strong inhibitor of CYP3A4: 400 mg daily for 7 days) with single dose of DAURISMO (200 mg) increased the glasdegib AUCinf by 2.4-fold (90% CI: 2.1, 2.7) and Cmax by 1.4-fold
Page: 11.0
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:145428
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:145428
ChemicalBook
CB82658197
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB82658197
MolPort
MolPort-035-789-706
https://www.molport.com/shop/molecule-link/MolPort-035-789-706
ZINC
ZINC000068251434
http://zinc15.docking.org/substances/ZINC000068251434
PubMed

PubMed

TitleDatePubMed
Patents

Patents

08148401
4
08431597
4
20090005416
4
20120157495
4

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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:37:59 GMT 2023
Edited
by admin
on Sat Dec 16 01:37:59 GMT 2023
Record UNII
K673DMO5H9
Record Status Validated (UNII)
Record Version
  • Download
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 [MI]
Common Name English
PF-04449913
Code English
PF-4449913
Code English
Glasdegib [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2189
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
FDA ORPHAN DRUG 608617
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
FDA ORPHAN DRUG 585517
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
NDF-RT N0000184149
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
Code System Code Type Description
LACTMED
Glasdegib
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
ChEMBL
CHEMBL2043437
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
DAILYMED
K673DMO5H9
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
NCI_THESAURUS
C84862
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
USAN
AB-120
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
EPA CompTox
DTXSID201025881
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
DRUG CENTRAL
5304
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
MERCK INDEX
m12133
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
EVMPD
SUB179278
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
CHEBI
145428
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
DRUG BANK
DB11978
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
FDA UNII
K673DMO5H9
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
INN
9930
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
PUBCHEM
25166913
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
SMS_ID
100000164688
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
PRIMARY
WIKIPEDIA
Glasdegib
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
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RXCUI
2105845
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
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CAS
1095173-27-5
Created by admin on Sat Dec 16 01:37:59 GMT 2023 , Edited by admin on Sat Dec 16 01:37:59 GMT 2023
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Related Record Type Details
Structure of GLASDEGIB HYDROCHLORIDE
SALT/SOLVATE -> PARENT
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
Structure of GLASDEGIB MALEATE
SALT/SOLVATE -> PARENT
Structure of GLASDEGIB
EXCRETED UNCHANGED
Following a single oral dose of 100 mg radiolabeled glasdegib, 49% of the administered dose was eliminated in the urine (17% unchanged), and 42% was eliminated in the feces (20% unchanged).
FECAL; URINE
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1
TRANSPORTER -> INHIBITOR
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
Glasdegib is 91% bound to human plasma proteins in vitro
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Glasdegib is metabolized primarily by the CYP3A4 pathway.
MAJOR
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
Structure of GLASDEGIB DIHYDROCHLORIDE
SALT/SOLVATE -> PARENT
MATE-2
TRANSPORTER -> INHIBITOR
SMOOTHENED HOMOLOG
TARGET -> INHIBITOR
COMPETITIVE INHIBITOR
IC50
CYTOCHROME P450 2C8
METABOLIC ENZYME -> SUBSTRATE
Glasdegib is metabolized primarily by the CYP3A4 pathway, with minor contributions by CYP2C8 and UGT1A9
MINOR
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9
METABOLIC ENZYME -> SUBSTRATE
Glasdegib is metabolized primarily by the CYP3A4 pathway, with minor contributions by CYP2C8 and UGT1A9
MINOR
Related Record Type Details
Structure of GLASDEGIB N-OXIDE
METABOLITE -> PARENT
Glasdegib was the most abundant circulating component in plasma, constituting 69% of plasma radioactivity, with minor circulating metabolites each being <8% of radioactivity.
Structure of 1-((2R,4S)-2-(1H-BENZIMIDAZOL-2-YL)-1-METHYL-3,4-DIHYDRO-2H-PYRIDIN-4-YL)-3-(4-CYANOPHENYL)UREA
METABOLITE -> PARENT
Glasdegib was the most abundant circulating component in plasma, constituting 69% of plasma radioactivity, with minor circulating metabolites each being <8% of radioactivity.
Structure of N-DESMETHYL GLASDEGIB
METABOLITE -> PARENT
Glasdegib was the most abundant circulating component in plasma, constituting 69% of plasma radioactivity, with minor circulating metabolites each being <8% of radioactivity.
Structure of 4-(((2R,4R)-2-(1H-BENZIMIDAZOL-2-YL)-1-METHYL-4-PIPERIDYL)CARBAMOYLAMINO)BENZAMIDE
METABOLITE -> PARENT
Glasdegib was the most abundant circulating component in plasma, constituting 69% of plasma radioactivity, with minor circulating metabolites each being <8% of radioactivity.
Related Record Type Details
Structure of GLASDEGIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ONCE DAILY DOSING

Tmax PHARMACOKINETIC ONCE DAILY DOSING

Volume of Distribution PHARMACOKINETIC
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