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
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-
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19552433 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1220 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10500 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25262379 |
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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
inconclusive [IC50 21.3174 uM] | ||||
no | ||||
yes [IC50 0.4176 uM] | ||||
yes [IC50 0.6619 uM] | ||||
yes [IC50 1.6933 uM] | ||||
yes [IC50 15.0916 uM] | ||||
yes [IC50 2.6837 uM] | ||||
yes [IC50 6.0081 uM] | ||||
yes [IC50 8.4866 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
major | ||||
major | ||||
major | ||||
minor | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
A phase I study of PF-04929113 (SNX-5422), an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumor malignancies and lymphomas. | 2011 Nov 1 |
|
Phase I dose-escalation studies of SNX-5422, an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumours. | 2014 Nov |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23763921
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19552433
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)
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SALT/SOLVATE (PARENT)
SUBSTANCE RECORD