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

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	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
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

Targets

Primary Target	Pharmacology	Potency
PI3-kinase p110-alpha subunit 41	Inhibitor 8,504	0.4 nM [IC50]
PI3-kinase p110-gamma subunit 32	Inhibitor 8,504	5.4 nM [IC50]
Serine/threonine-protein kinase mTOR 35	Inhibitor 8,504	1.6 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute myeloid leukemia 141	Primary	Phase II 1,147	Unknown
Metastatic colorectal cancer 14	Primary	Phase II 1,147	Unknown
Endometrial cancer 44	Primary	Phase II 1,147	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4759 ng/mL	130 mg 1 times / week multiple, intravenous		GEDATOLISIB plasma	Homo sapiens
6279 ng/mL	154 mg 1 times / week multiple, intravenous	PD-0325901	GEDATOLISIB plasma	Homo sapiens
6558 ng/mL	89 mg single, intravenous		GEDATOLISIB plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
9277 ng × h/mL	130 mg 1 times / week multiple, intravenous		GEDATOLISIB plasma	Homo sapiens
14230 ng × h/mL	154 mg 1 times / week multiple, intravenous	PD-0325901	GEDATOLISIB plasma	Homo sapiens
8647 ng × h/mL	89 mg single, intravenous		GEDATOLISIB plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
29.23 h	130 mg 1 times / week multiple, intravenous		GEDATOLISIB plasma	Homo sapiens
29.63 h	154 mg 1 times / week multiple, intravenous	PD-0325901	GEDATOLISIB plasma	Homo sapiens
36.92 h	89 mg single, intravenous		GEDATOLISIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.7%	89 mg single, intravenous		GEDATOLISIB plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
319 mg 1 times / week multiple, intravenous Highest studied dose	unhealthy, ADULT	DLT: Mucosal inflammation, skin rash...
154 mg 1 times / week multiple, intravenous MTD	unhealthy, ADULT	DLT: Mucosal inflammation, AST increased...
222 mg 1 times / week multiple, intravenous Studied dose	unhealthy, ADULT	DLT: Mucosal inflammation... Other AEs: ALT increased, Mucosal inflammation...
266 mg 1 times / week multiple, intravenous Studied dose	unhealthy, ADULT	DLT: Skin rash, Mucosal inflammation...

Showing 1 to 4 of 4 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Mucosal inflammation	grade 3, 25% DLT	319 mg 1 times / week multiple, intravenous Highest studied dose	unhealthy, ADULT
skin rash	grade 3, 25% DLT	319 mg 1 times / week multiple, intravenous Highest studied dose	unhealthy, ADULT
ALT increased	2.4% DLT	154 mg 1 times / week multiple, intravenous MTD	unhealthy, ADULT
AST increased	2.4% DLT	154 mg 1 times / week multiple, intravenous MTD	unhealthy, ADULT
Mucosal inflammation	grade 3, 2.4% DLT, Disc. AE	154 mg 1 times / week multiple, intravenous MTD	unhealthy, ADULT

Showing 1 to 5 of 12 entries

Previous1 2 3Next

Sourcing

Sourcing

Show entries

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

Showing 1 to 5 of 30 entries

Previous1 2 3 4 5 6Next

PubMed

Show entries

Title	Date	PubMed
		252160469
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	20166697
PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor.	2010 Oct 1	20797855
Identification of 2-oxatriazines as highly potent pan-PI3K/mTOR dual inhibitors.	2011 Aug 15	21763134

Showing 1 to 4 of 4 entries

Previous1Next

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
Record UNII	96265TNH2R
Record Status	`Validated (UNII)`
Record Version

Show entries

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

Showing 1 to 5 of 9 entries

Previous1 2Next

Show entries

Classification Tree

Code System

Code

Angiogenesis Inhibitor

NCI_THESAURUS

C2152

Antineoplastic Protein Inhibitor

NCI_THESAURUS

C129825

Showing 1 to 2 of 2 entries

Previous1Next

Show entries

Code System

Code

Type

Description

NCI_THESAURUS

C91732

PRIMARY

FDA UNII

96265TNH2R

PRIMARY

PUBCHEM

44516953

PRIMARY

SMS_ID

100000174860

PRIMARY

CAS

1197160-78-3

PRIMARY

Showing 1 to 5 of 11 entries

Previous1 2 3Next

Show entries

Related Record

Type

Details


					JQ83GG8LT2

PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT ALPHA ISOFORM

TARGET -> INHIBITOR

Showing 1 to 1 of 1 entries

Previous1Next

Show entries

Related Record

Type

Details


					96265TNH2R

GEDATOLISIB

ACTIVE MOIETY

Showing 1 to 1 of 1 entries

Previous1Next

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound