SNX-5422

Investigational

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 Search

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
Sources: http://www.enogene.com/uploads/b6671ecd284a357cb6c967e1ce85f653-1/files/E1KS2656.pdf
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

Primary Target	Pharmacology	Condition	Potency
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19552433	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Solid tumors 145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21908572	Primary	Phase I 428	Unknown Approved Use Unknown
Lymphomas 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21908572	Primary	Phase I 428	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18948577	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYPs 22	P-gp 1537 CYP2E1 667 CYP2B6 664 CYP2C8 693 CYP3A5 395 CYP1B1 92 CYP1A1 349 CYP1A2 1054 CYP2C19 991

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363680138	inconclusive [IC50 21.3174 uM]	SNX-2112 1
CYPs 28	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19552433/	no	SNX-2112 1
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007063	yes [IC50 0.4176 uM]	SNX-2112 1
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006332	yes [IC50 0.6619 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681366	yes [IC50 1.6933 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681366	yes [IC50 15.0916 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681366	yes [IC50 2.6837 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680138	yes [IC50 6.0081 uM]	SNX-2112 1
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680138	yes [IC50 8.4866 uM]	SNX-2112 1

Drug as victim

Target	Modality	Activity	Metabolite
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	major	SNX-2112 1
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	major	SNX-2112 1
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	major	SNX-2112 1
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	major	SNX-2112 1
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	minor	SNX-2112 1
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	minor	SNX-2112 1
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	minor	SNX-2112 1
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	no	SNX-2112 1
CYP1B1 92	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	no	SNX-2112 1
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	no	SNX-2112 1
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	no	SNX-2112 1
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24191862/	yes	SNX-2112 1

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00H1AJ	https://www.1pchem.com/search?query=1P00H1AJ
Excenen	EX-A2343	http://www.excenen.com/searchresultlist.php?id=EX-A2343
Lab Seeker	SC-85704	http://www.labseeker.com/search.php?keywords=SC-85704&category=0
LabSeeker	SC-85704	http://www.labseeker.com/search.php?keywords=SC-85704&category=0
MolPort	MolPort-042-652-831	https://www.molport.com/shop/molecule-link/MolPort-042-652-831
MolPort	MolPort-046-594-257	https://www.molport.com/shop/molecule-link/MolPort-046-594-257
Molnova	M10581	https://www.molnova.com/en/serch-list.html?keywords=M10581
MuseChem	I008668	https://www.musechem.com/product/I008668.html
Selleck Chemicals	S2656	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2656
TargetMol	T4342	https://www.targetmol.com/search?keyword=T4342
TargetMol	T6341	https://www.targetmol.com/search?keyword=T6341
Toronto Research Chemicals	P293780	https://www.trc-canada.com/product-detail/?CatNum=P293780
eMolecules	37153197	https://orderbb.emolecules.com/search/#?query=37153197
eMolecules	49227219	https://orderbb.emolecules.com/search/#?query=49227219

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

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

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 GMT 2023` Edited by `admin` on `Sat Dec 16 01:47:05 GMT 2023`
Record UNII	BF52J69Q8T
Record Status	`Validated (UNII)`
Record Version

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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