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Details

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

Description

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.

Originator

Approval Year

Unknown
99263
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7468
Leukemia, Myeloid, Acute
 0.4 nM [IC50]
Inhibitor
7468
Leukemia, Myeloid, Acute
 1.6 nM [IC50]
Inhibitor
7468
Leukemia, Myeloid, Acute
 5.4 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Serine/threonine-protein kinase mTOR
PI3-kinase p110-gamma subunit
PI3-kinase p110-alpha subunit
Phase II
1079
Primary
Serine/threonine-protein kinase mTOR
PI3-kinase p110-gamma subunit
PI3-kinase p110-alpha subunit
Phase II
1079
Primary
Serine/threonine-protein kinase mTOR
PI3-kinase p110-gamma subunit
PI3-kinase p110-alpha subunit
Phase II
1079
PubMed

PubMed

TitleDatePubMed
Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor.
2010 Mar 25
PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor.
2010 Oct 1
Identification of 2-oxatriazines as highly potent pan-PI3K/mTOR dual inhibitors.
2011 Aug 15
Patents

Patents

8039469
2
JP2010215620A
1
JP2011522802A
28
US2011257167
1
US2013158023
1
US2016166546
1
US2016220537
2

Sample Use Guides

In Vivo Use Guide
154mg IV weekly
Route of Administration: Intravenous
In Vitro Use Guide
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 Mon Oct 21 21:16:01 UTC 2019
Edited
by admin
on Mon Oct 21 21:16:01 UTC 2019
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 Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
Code System Code Type Description
NCI_THESAURUS
C91732
Created by admin on Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
PRIMARY
PUBCHEM
44516953
Created by admin on Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
PRIMARY
CAS
1197160-78-3
Created by admin on Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
PRIMARY
INN
9984
Created by admin on Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
PRIMARY
EPA CompTox
1197160-78-3
Created by admin on Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
PRIMARY
ChEMBL
CHEMBL592445
Created by admin on Mon Oct 21 21:16:01 UTC 2019 , Edited by admin on Mon Oct 21 21:16:01 UTC 2019
PRIMARY
Related Record Type Details
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT ALPHA ISOFORM
TARGET -> INHIBITOR
Related Record Type Details
Structure of GEDATOLISIB
ACTIVE MOIETY
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