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.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.4 nM [IC50]
Inhibitor
8297
 5.4 nM [IC50]
Inhibitor
8297
 1.6 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
Page: p.6, 17
DLT: Mucosal inflammation, skin rash...
Dose limiting toxicities:
Mucosal inflammation (grade 3, 25%)
skin rash (grade 3, 25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
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:
https://pubmed.ncbi.nlm.nih.gov/25652454
Page: p.6, 17
Sourcing

Sourcing

Vendor/AggregatorIDURL
1PlusChem LLC
1P000PYM
https://www.1pchem.com/search?query=1P000PYM
AChemBlock
10363
http://www.achemblock.com/catalogsearch/result/?q=10363
AK Scientific
X7445
https://aksci.com/item_detail.php?cat=X7445
Angene
AGN-PC-076USO
http://www.angenechemical.com/productshow/AGN-PC-076USO.html
ApexBio Technology
B2179
https://www.apexbt.com/catalogsearch/result/?q=B2179
AstaTech
42561
http://astatechinc.com/CPSResult.php?CRNO=42561
Axon MedChem
1807
https://www.axonmedchem.com/product/1807
BLD Pharm
BD328410
http://www.bldpharm.com/search/Search.html?keyword=BD328410
BOC Sciences
1197160-78-3
http://www.bocsci.com/description.asp?cas=1197160-78-3
Capot Chemical
19144
https://www.capotchem.com/search.do?q=19144
Cayman Chemical
14567
http://www.caymanchem.com/app/template/Product.vm/catalog/14567
ChemShuttle
104819
https://www.chemshuttle.com/catalogsearch/result/?q=104819
Excenen
EX-A028
http://www.excenen.com/searchresultlist.php?id=EX-A028
Hairui
GESA042
http://www.hairuichem.com/en/product/search.do?q=GESA042
KeyOrganics
FE-0013
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=FE-0013
Lab Seeker
SC-85781
http://www.labseeker.com/search.php?keywords=SC-85781&category=0
LabSeeker
SC-85781
http://www.labseeker.com/search.php?keywords=SC-85781&category=0
Matrix Scientific
145213
http://www.matrixscientific.com/145213.html
MolPort
MolPort-009-194-127
https://www.molport.com/shop/molecule-link/MolPort-009-194-127
Molnova
M10696
https://www.molnova.com/en/serch-list.html?keywords=M10696
Selleck Chemicals
S2628
http://www.selleckchem.com/search.html?searchDTO.searchParam=S2628
ShangHai Biochempartner
BCP000223
http://www.biochempartner.com/search_BCP000223
ShangHai Biochempartner
BCP01986
http://www.biochempartner.com/search_BCP01986
TargetMol
T1970
https://www.targetmol.com/search?keyword=T1970
Tocris
4823
https://www.tocris.com/search.php?Type=QuickSearch&Value=4823
Toronto Research Chemicals
D461135
https://www.trc-canada.com/product-detail/?CatNum=D461135
W&J PharmaChem
50C1562554
http://wjpharmachem.com/new/searcht.php?keyword=50C1562554
eMolecules
36516877
https://orderbb.emolecules.com/search/#?query=36516877
eNovation Chemicals
D572839
https://www.enovationchem.com/Products.asp?SEARCHTEXT=D572839&searchbtn.x=0&searchbtn.y=0
mcule
MCULE-2058637166
https://mcule.com/MCULE-2058637166/
PubMed

PubMed

TitleDatePubMed
PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor.
2010 Oct 1
Patents

Patents

08039469
2
JP2010215620A
1
JP2011522802A
30
US2011257167
1
US2013158023
1
US2016166546
3
US2016220537
5

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 Sat Dec 16 17:56:11 GMT 2023
Edited
by admin
on Sat Dec 16 17:56:11 GMT 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 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C91732
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
FDA UNII
96265TNH2R
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
PUBCHEM
44516953
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
SMS_ID
100000174860
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
CAS
1197160-78-3
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
INN
9984
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
EPA CompTox
DTXSID40152557
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
ChEMBL
CHEMBL592445
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
DRUG BANK
DB11896
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
USAN
AB-113
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
PRIMARY
WIKIPEDIA
Gedatolisib
Created by admin on Sat Dec 16 17:56:11 GMT 2023 , Edited by admin on Sat Dec 16 17:56:11 GMT 2023
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
NIH
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