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Details

Stereochemistry ACHIRAL
Molecular Formula C25H30F3N5O4
Molecular Weight 521.532
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SNX-5422

SMILES

CC1(C)CC2=C(C(=NN2C3=CC(N[C@H]4CC[C@@H](CC4)OC(=O)CN)=C(C=C3)C(N)=O)C(F)(F)F)C(=O)C1

InChI

InChIKey=AVDSOVJPJZVBTC-CTYIDZIISA-N
InChI=1S/C25H30F3N5O4/c1-24(2)10-18-21(19(34)11-24)22(25(26,27)28)32-33(18)14-5-8-16(23(30)36)17(9-14)31-13-3-6-15(7-4-13)37-20(35)12-29/h5,8-9,13,15,31H,3-4,6-7,10-12,29H2,1-2H3,(H2,30,36)/t13-,15-

HIDE SMILES / InChI

Molecular Formula C25H30F3N5O4
Molecular Weight 521.532
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including

SNX-5422 (also known as PF-04929113) is a synthetic, novel, small molecule Hsp90 inhibitor with potential antineoplastic activity. Hsp90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation or immune responses. Inhibition of Hsp90 by SNX-2112 may result in the proteasome degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation. SNX-5422 is originally developed by Pfizer and Serenex, Inc., and the phase I clinical trials for it has been completed in the treatment of solid tumors. Although the mechanism of action remains to be fully elucidated, SNX-5422, which is a prodrug, is rapidly converted to SNX-2112 that accumulates in tumors relative to normal tissues.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1220 ng/mL
100 mg/m² 1 times / 2 days steady-state, oral
dose: 100 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
579 ng/mL
50 mg/m² 1 times / day steady-state, oral
dose: 50 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
723 mg/mL
67 mg/m² 1 times / day steady-state, oral
dose: 67 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
770 ng/mL
56 mg/m² 1 times / 2 days steady-state, oral
dose: 56 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
460 ng/mL
21.28 mg/m² 1 times / 2 days steady-state, oral
dose: 21.28 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10500 ng × h/mL
100 mg/m² 1 times / 2 days steady-state, oral
dose: 100 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3950 ng × h/mL
50 mg/m² 1 times / day steady-state, oral
dose: 50 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5770 ng × h/mL
67 mg/m² 1 times / day steady-state, oral
dose: 67 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6010 ng × h/mL
56 mg/m² 1 times / 2 days steady-state, oral
dose: 56 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6610 ng × h/mL
21.28 mg/m² 1 times / 2 days steady-state, oral
dose: 21.28 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.2 h
100 mg/m² 1 times / 2 days steady-state, oral
dose: 100 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11.1 h
50 mg/m² 1 times / day steady-state, oral
dose: 50 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9.8 h
67 mg/m² 1 times / day steady-state, oral
dose: 67 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10.9 h
56 mg/m² 1 times / 2 days steady-state, oral
dose: 56 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
16.8 h
21.28 mg/m² 1 times / 2 days steady-state, oral
dose: 21.28 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SNX-2112 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
OverviewDrug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Phase I trial of the HSP90 inhibitor PF-04929113 (SNX5422) in adult patients with recurrent, refractory hematologic malignancies.
2013 Aug
Phase I dose-escalation studies of SNX-5422, an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumours.
2014 Nov
Patents

Sample Use Guides

refractory hematologic malignancies: was administered orally every other day for 21 days of a 28-day cycle. Twenty-five patients were treated, with dose escalation ranging from 5.32 mg/m(2) to 74 mg/m(2) using a 3 plus 3 trial design.
Route of Administration: Oral
PF-04929113 (SNX-5422) exhibits potent effects on Her-2 stability and causes expected up-regulation of Hsp70. PF-04929113 shows potent antiproliferative activity against a broad range of cancer cell types, e.g. MCF-7 (IC50=16 nM), SW620 (IC50=19 nM), K562 (IC50=23 nM), SK-MEL-5 (IC50=25 nM), and A375 (IC50=51 nM)
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:47:05 UTC 2023
Edited
by admin
on Sat Dec 16 01:47:05 UTC 2023
Record UNII
BF52J69Q8T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SNX-5422
Common Name English
GLYCINE, TRANS-4-((2-(AMINOCARBONYL)-5-(4,5,6,7-TETRAHYDRO-6,6-DIMETHYL-4-OXO-3-(TRIFLUOROMETHYL)-1H-INDAZOL-1-YL)PHENYL)AMINO)CYCLOHEXYL ESTER
Common Name English
SNX 5422 [WHO-DD]
Common Name English
PF-04929113
Common Name English
PF-4929113
Common Name English
Code System Code Type Description
SMS_ID
100000175508
Created by admin on Sat Dec 16 01:47:05 UTC 2023 , Edited by admin on Sat Dec 16 01:47:05 UTC 2023
PRIMARY
DRUG BANK
DB06070
Created by admin on Sat Dec 16 01:47:05 UTC 2023 , Edited by admin on Sat Dec 16 01:47:05 UTC 2023
PRIMARY
FDA UNII
BF52J69Q8T
Created by admin on Sat Dec 16 01:47:05 UTC 2023 , Edited by admin on Sat Dec 16 01:47:05 UTC 2023
PRIMARY
EPA CompTox
DTXSID50238270
Created by admin on Sat Dec 16 01:47:05 UTC 2023 , Edited by admin on Sat Dec 16 01:47:05 UTC 2023
PRIMARY
NCI_THESAURUS
C141504
Created by admin on Sat Dec 16 01:47:05 UTC 2023 , Edited by admin on Sat Dec 16 01:47:05 UTC 2023
PRIMARY
PUBCHEM
44195571
Created by admin on Sat Dec 16 01:47:05 UTC 2023 , Edited by admin on Sat Dec 16 01:47:05 UTC 2023
PRIMARY
CAS
908115-27-5
Created by admin on Sat Dec 16 01:47:05 UTC 2023 , Edited by admin on Sat Dec 16 01:47:05 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT