GEDATOLISIB

Investigational

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21325073
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

Targets

Primary Target	Pharmacology	Potency
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21325073 \| https://www.ncbi.nlm.nih.gov/pubmed/20166697	Inhibitor 8504	0.4 nM [IC50]
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20166697	Inhibitor 8504	5.4 nM [IC50]
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20166697	Inhibitor 8504	1.6 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute myeloid leukemia 141 Sources: https://clinicaltrials.gov/ct2/show/NCT02438761	Primary	Phase II 1147	Unknown Approved Use Unknown
Metastatic colorectal cancer 14 Sources: https://clinicaltrials.gov/ct2/show/NCT01925274	Primary	Phase II 1147	Unknown Approved Use Unknown
Endometrial cancer 44 Sources: https://clinicaltrials.gov/ct2/show/NCT01420081	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4759 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29067643/	130 mg 1 times / week multiple, intravenous dose: 130 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		GEDATOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6279 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29067643/	154 mg 1 times / week multiple, intravenous dose: 154 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PD-0325901	PD-0325901	GEDATOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6558 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30256541	89 mg single, intravenous dose: 89 mg route of administration: Intravenous experiment type: SINGLE co-administered:		GEDATOLISIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
9277 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29067643/	130 mg 1 times / week multiple, intravenous dose: 130 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		GEDATOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14230 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29067643/	154 mg 1 times / week multiple, intravenous dose: 154 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PD-0325901	PD-0325901	GEDATOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8647 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30256541	89 mg single, intravenous dose: 89 mg route of administration: Intravenous experiment type: SINGLE co-administered:		GEDATOLISIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
29.23 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29067643/	130 mg 1 times / week multiple, intravenous dose: 130 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		GEDATOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
29.63 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29067643/	154 mg 1 times / week multiple, intravenous dose: 154 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PD-0325901	PD-0325901	GEDATOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
36.92 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30256541	89 mg single, intravenous dose: 89 mg route of administration: Intravenous experiment type: SINGLE co-administered:		GEDATOLISIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.7% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30256541	89 mg single, intravenous dose: 89 mg route of administration: Intravenous experiment type: SINGLE co-administered:		GEDATOLISIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse 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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454	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
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454	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
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454	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
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454	DLT: Skin rash, Mucosal inflammation... Dose limiting toxicities: Skin rash (grade 3, 12.5%) Mucosal inflammation (grade 3, 12.5%) Hyperglycemia (grade 3, 12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/25652454

AEs

AE	Significance	Dose	Population
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25652454

Sourcing

Vendor/Aggregator	ID	URL
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
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
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
mcule	MCULE-2058637166	https://mcule.com/MCULE-2058637166/
Molnova	M10696	https://www.molnova.com/en/serch-list.html?keywords=M10696
MolPort	MolPort-009-194-127	https://www.molport.com/shop/molecule-link/MolPort-009-194-127
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

PubMed

Title	Date	PubMed
Identification of 2-oxatriazines as highly potent pan-PI3K/mTOR dual inhibitors.	2011-08-15	21763134
PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor.	2010-10-01	20797855
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.	2010-03-25	20166697

Patents

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 `Wed Apr 02 09:49:52 GMT 2025` Edited by `admin` on `Wed Apr 02 09:49:52 GMT 2025`
Record UNII	96265TNH2R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GEDATOLISIB

Official Name

English

gedatolisib [INN]

Preferred 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

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