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

Details

Stereochemistry ACHIRAL
Molecular Formula C32H41N9O4
Molecular Weight 615.7258
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GEDATOLISIB

SMILES

CN(C)C1CCN(CC1)C(=O)C2=CC=C(NC(=O)NC3=CC=C(C=C3)C4=NC(=NC(=N4)N5CCOCC5)N6CCOCC6)C=C2

InChI

InChIKey=DWZAEMINVBZMHQ-UHFFFAOYSA-N
InChI=1S/C32H41N9O4/c1-38(2)27-11-13-39(14-12-27)29(42)24-5-9-26(10-6-24)34-32(43)33-25-7-3-23(4-8-25)28-35-30(40-15-19-44-20-16-40)37-31(36-28)41-17-21-45-22-18-41/h3-10,27H,11-22H2,1-2H3,(H2,33,34,43)

HIDE SMILES / InChI

Molecular Formula C32H41N9O4
Molecular Weight 615.7258
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.pharmacodia.com/yaodu/html/v1/chemicals/0d8f8313c83e69d101e8997d3065fbff.html https://www.ncbi.nlm.nih.gov/pubmed/22261591

Gedatolisib (PF-05212384, PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ and mTOR, originally being developed by Wyeth. Upon intravenous administration, gedatolisib inhibits both PI3K and mTOR kinases, which may result in apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K. Significant antitumor efficacy and a favorable pharmacokinetic/safety profile justified clinical evaluation of Gedatolisib. Gedatolisb is in phase II clinical trials by Pfizer for the treatment of acute myeloid leukaemia. Gedatolisb is in phase I clinical trials for the treatment of solid tumours.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
319 mg 1 times / week multiple, intravenous
Highest studied dose
Dose: 319 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 319 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.6, 17
DLT: Mucosal inflammation, skin rash...
Dose limiting toxicities:
Mucosal inflammation (grade 3, 25%)
skin rash (grade 3, 25%)
Sources: Page: p.6, 17
154 mg 1 times / week multiple, intravenous
MTD
Dose: 154 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 154 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 42
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 42
Sources: Page: p.6, 17
DLT: Mucosal inflammation, AST increased...
Dose limiting toxicities:
Mucosal inflammation (grade 3, 2.4%)
AST increased (2.4%)
ALT increased (2.4%)
Sources: Page: p.6, 17
222 mg 1 times / week multiple, intravenous
Studied dose
Dose: 222 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 222 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6, 17
DLT: Mucosal inflammation...
Other AEs: ALT increased, Mucosal inflammation...
Dose limiting toxicities:
Mucosal inflammation (grade 3, 42.9%)
Other AEs:
ALT increased (grade 2, 14.3%)
Mucosal inflammation (grade 3, 14.3%)
Inflammation of mout (grade 3, 14.3%)
Sources: Page: p.6, 17
266 mg 1 times / week multiple, intravenous
Studied dose
Dose: 266 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 266 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.6, 17
DLT: Skin rash, Hyperglycemia...
Dose limiting toxicities:
Skin rash (grade 3, 12.5%)
Hyperglycemia (grade 3, 12.5%)
Mucosal inflammation (grade 3, 12.5%)
Sources: Page: p.6, 17
AEs

AEs

AESignificanceDosePopulation
Mucosal inflammation grade 3, 25%
DLT
319 mg 1 times / week multiple, intravenous
Highest studied dose
Dose: 319 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 319 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.6, 17
skin rash grade 3, 25%
DLT
319 mg 1 times / week multiple, intravenous
Highest studied dose
Dose: 319 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 319 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources: Page: p.6, 17
ALT increased 2.4%
DLT
154 mg 1 times / week multiple, intravenous
MTD
Dose: 154 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 154 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 42
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 42
Sources: Page: p.6, 17
AST increased 2.4%
DLT
154 mg 1 times / week multiple, intravenous
MTD
Dose: 154 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 154 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 42
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 42
Sources: Page: p.6, 17
Mucosal inflammation grade 3, 2.4%
DLT, Disc. AE
154 mg 1 times / week multiple, intravenous
MTD
Dose: 154 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 154 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 42
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 42
Sources: Page: p.6, 17
ALT increased grade 2, 14.3%
222 mg 1 times / week multiple, intravenous
Studied dose
Dose: 222 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 222 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6, 17
Inflammation of mout grade 3, 14.3%
222 mg 1 times / week multiple, intravenous
Studied dose
Dose: 222 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 222 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6, 17
Mucosal inflammation grade 3, 14.3%
222 mg 1 times / week multiple, intravenous
Studied dose
Dose: 222 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 222 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6, 17
Mucosal inflammation grade 3, 42.9%
DLT
222 mg 1 times / week multiple, intravenous
Studied dose
Dose: 222 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 222 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.6, 17
Hyperglycemia grade 3, 12.5%
DLT
266 mg 1 times / week multiple, intravenous
Studied dose
Dose: 266 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 266 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.6, 17
Mucosal inflammation grade 3, 12.5%
DLT
266 mg 1 times / week multiple, intravenous
Studied dose
Dose: 266 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 266 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.6, 17
Skin rash grade 3, 12.5%
DLT
266 mg 1 times / week multiple, intravenous
Studied dose
Dose: 266 mg, 1 times / week
Route: intravenous
Route: multiple
Dose: 266 mg, 1 times / week
Sources: Page: p.6, 17
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.6, 17
Sourcing

Sourcing

Vendor/AggregatorIDURL

Sample Use Guides

154mg IV weekly
Route of Administration: Intravenous
In vitro, Gedatolisib potently inhibited class I PI3Ks (IC(50) vs. PI3K-α = 0.4 nmol/L), PI3K-α mutants, and mTOR. Gedatolisib inhibited growth of 50 diverse human tumor cell lines at IC(50) values of less than 100 nmol/L.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:56:11 UTC 2023
Edited
by admin
on Sat Dec 16 17:56:11 UTC 2023
Record UNII
96265TNH2R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GEDATOLISIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
1-(4-(4-(DIMETHYLAMINO)PIPERIDINE-1-CARBONYL)PHENYL)-3-(4-(4,6-DIMORPHOLINO-1,3,5-TRIAZIN-2-YL)PHENYL)UREA
Systematic Name English
Gedatolisib [WHO-DD]
Common Name English
GEDATOLISIB [USAN]
Common Name English
gedatolisib [INN]
Common Name English
PF-05212384
Code English
UREA, N-(4-((4-(DIMETHYLAMINO)-1-PIPERIDINYL)CARBONYL)PHENYL)-N'-(4-(4,6-DI-4-MORPHOLINYL-1,3,5-TRIAZIN-2-YL)PHENYL)-
Systematic Name English
N-(4-((4-(DIMETHYLAMINO)-1-PIPERIDINYL)CARBONYL)PHENYL)-N'-(4-(4,6-DIMORPHOLIN-4-YL-1,3,5-TRIAZIN-2-YL)PHENYL)UREA
Systematic Name English
PKI-587
Code English
Classification Tree Code System Code
NCI_THESAURUS C2152
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C91732
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
FDA UNII
96265TNH2R
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
PUBCHEM
44516953
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
SMS_ID
100000174860
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
CAS
1197160-78-3
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
INN
9984
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
EPA CompTox
DTXSID40152557
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
ChEMBL
CHEMBL592445
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
DRUG BANK
DB11896
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
USAN
AB-113
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
WIKIPEDIA
Gedatolisib
Created by admin on Sat Dec 16 17:56:11 UTC 2023 , Edited by admin on Sat Dec 16 17:56:11 UTC 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY