Cat. No.: HY-184650

SHP2/NAMPT-IN-1

SHP2/NAMPT-IN-1 is an orally active dual inhibitor of SHP2 and NAMPT, with IC₅₀ values of 30.5 nM and 24.4 nM, respectively. SHP2/NAMPT-IN-1 reduces NAD⁺ levels and p-ERK expression by inhibiting NAMPT. SHP2/NAMPT-IN-1 can inhibit the migration and colony formation of MDA-MB-231 cells and promote apoptosis. SHP2/NAMPT-IN-1 has anti-proliferative activity against a variety of tumor cell lines and can reverse PD-L1-mediated T-cell immunosuppression. SHP2/NAMPT-IN-1 can be used for breast cancer research.

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Formule: C₂₄H₂₆ClN₇OS
Masse moléculaire:496.03

Stockage:

Please store the product under the recommended conditions in the Certificate of Analysis.

SHP2/NAMPT-IN-1 Chemical Structure

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Activité biologique
- Description
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Pureté et documentation
Références
Calculators
Help & FAQs
Bioz

Activité biologique

Description

Voir tous les produits spécifiques à Isoform ERK :

Cellular Effect

Cell Line	Type	Value	Description	References
KYSE-520 cell line	IC50	0.6 μM	Exhibits antiproliferative activity against KYSE520 cells for 72 h. Exhibits antiproliferative activity against KYSE520 cells for 72 h.	42324937
HT-29	IC50	1.4 μM	Exhibits antiproliferative activity against HT29 cells for 72 h. Exhibits antiproliferative activity against HT29 cells for 72 h.	42324937
MDA-MB-231	IC50	0.34 μM	Exhibits antiproliferative activity against MDA‑MB‑231 cells for 72 h. Exhibits antiproliferative activity against MDA‑MB‑231 cells for 72 h.	42324937
HepG2	IC50	2.9 μM	Exhibits antiproliferative activity against HepG2 cells for 72 h. Exhibits antiproliferative activity against HepG2 cells for 72 h.	42324937
HeLa	IC50	1.4 μM	Exhibits antiproliferative activity against HeLa cells for 72 h. Exhibits antiproliferative activity against HeLa cells for 72 h.	42324937
A549	IC50	0.7 μM	Exhibits antiproliferative activity against A549 cells for 72 h. Exhibits antiproliferative activity against A549 cells for 72 h.	42324937
MCF7	IC50	1.3 μM	Exhibits antiproliferative activity against MCF‑7 cells for 72 h. Exhibits antiproliferative activity against MCF‑7 cells for 72 h.	42324937
4T1	IC50	0.7 μM	Exhibits antiproliferative activity against 4T1 cells for 72 h. Exhibits antiproliferative activity against 4T1 cells for 72 h.	42324937

In Vitro

SHP2/NAMPT-IN-1 (Compound A4) exhibits potent inhibitory activity against SHP2 and NAMPT in cell-free enzyme assays (IC₅₀ = 30.5 nM and 24.4 nM, respectively), while showing no significant inhibition against SHP1, PTP1B, and NMNAT (IC₅₀ > 20 μM) ^[1].
SHP2/NAMPT-IN-1 (72 h) exhibits antiproliferative activity against multiple SHP099‑insensitive tumor cell lines, including KYSE520 (IC₅₀ = 0.6 μM), HT29 (IC₅₀ = 1.4 μM), MDA‑MB‑231 (IC₅₀ = 0.34 μM), HepG2 (IC₅₀ = 2.9 μM), HeLa (IC₅₀ = 1.4 μM), A549 (IC₅₀ = 0.7 μM), as well as breast cancer cells MCF‑7 (IC₅₀ = 1.3 μM) and 4T1 (IC₅₀ = 0.7 μM) ^[1].
SHP2/NAMPT-IN-1 (1 μM; 1 h) significantly enhances the thermal stability of SHP2 and NAMPT proteins in MDA‑MB‑231 cells in cellular thermal shift assay (CETSA), indicating that it binds to the target proteins^[1].
SHP2/NAMPT-IN-1 (0.5-2 μM; 24 h) dose‑dependently reduces phosphorylated ERK (p‑ERK) levels in MDA‑MB‑231 cells^[1].
SHP2/NAMPT-IN-1 (0.25-1 μM; 24 h) dose‑dependently reduces intracellular NAD^⁺ levels in MDA‑MB‑231 cells^[1].
SHP2/NAMPT-IN-1 (0.5-2 μM; 12 days) significantly inhibits colony formation in MDA‑MB‑231 cells^[1].
SHP2/NAMPT-IN-1 (0.5-2 μM; 24 h) induces apoptosis in MDA‑MB‑231 cells, with apoptosis rates of 31.6% and 38.9%, respectively^[1].
SHP2/NAMPT-IN-1 (0.5-2 μM; 24 h) upregulates the pro‑apoptotic protein Bax and downregulates the anti‑apoptotic protein Bcl‑2 in MDA‑MB‑231 cells^[1].
SHP2/NAMPT-IN-1 (0.5-2 μM; 24-48 h) significantly inhibits cell migration in wound healing and Transwell migration assays in MDA‑MB‑231 cells^[1].
SHP2/NAMPT-IN-1 (0.25-1 μM; 72 h) dose‑dependently reverses PD‑L1‑mediated immunosuppression and promotes IFN‑γ and IL‑2 secretion in Jurkat T cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 cells
Concentration:

0.5, 1, 2 μM
Incubation Time:

24 h
Result:

Dose-dependently reduced the levels of phosphorylated ERK (p-ERK).

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 cells
Concentration:

0.5, 2 μM
Incubation Time:

24 h
Result:

Upregulated the pro-apoptotic protein Bax and downregulated the anti-apoptotic protein Bcl-2.

Cell Proliferation Assay^[1]

Cell Line:

MDA-MB-231 cells
Concentration:

0.5, 2 μM
Incubation Time:

12 days
Result:

Significantly inhibited colony formation, showing superior efficacy over the combination of FK866 and SHP099.

Apoptosis Analysis^[1]

Cell Line:

MDA-MB-231 cells
Concentration:

0.5, 2 μM
Incubation Time:

24 h
Result:

Induced apoptosis with rates of 31.6% (at 0.5 μM) and 38.9% (at 2 μM), higher than the FK866/SHP099 combination (22.7%).

Cell Migration Assay ^[1]

Cell Line:

MDA-MB-231 cells
Concentration:

0.5, 2 μM
Incubation Time:

24 and 48 h
Result:

Significantly delayed wound closure and inhibited cell migration.

Cell Migration Assay ^[1]

Cell Line:

MDA-MB-231 cells
Concentration:

0.5, 2 μM
Incubation Time:

48 h
Result:

Significantly inhibited cell migration, with superior efficacy over FK866 or SHP099 alone.

ELISA Assay^[1]

Cell Line:

Jurkat cells
Concentration:

0.25, 0.5, 1 μM
Incubation Time:

72 h
Result:

Dose‑dependently reverses PD‑L1‑mediated immunosuppression and promotes IFN‑γ and IL‑2 secretion in Jurkat T cells.

Parmacokinetics

Species	Dose	Route	AUC_0-t	C_max	T_max	T_1/2	F
Rat^[1]	10 mg/kg	p.o.	1158 ng·h/mL	617 ng/mL	0.9 h	2.9 h	37 %
Rat^[1]	2 mg/kg	i.v.	626 ng·h/mL	327 ng/mL	0.03 h	2.2 h	/

In Vivo

SHP2/NAMPT-IN-1 (Compound A4) (5, 10, 20 mg/kg; orally; once daily; for 15 days) dose-dependently suppresses tumor growth without causing body weight loss in an MDA-MB-231 xenograft BALB/c nude mouse model^[1].
SHP2/NAMPT-IN-1 (10 mg/kg; orally; once daily; for 15 days) suppresses tumor growth and significantly increases CD8⁺ cytotoxic T-cell infiltration in tumor tissues in a 4T1 syngeneic immunocompetent BALB/c mouse model, and the combination with anti-PD-1 antibody (HY-P99144) significantly enhances the TGI^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female BALB/c nude mice (6-8 weeks old) or immunocompetent female BALB/c mice were inoculated subcutaneously in the right flank with 5 × 10⁵ MDA-MB-231^[1].
Dosage:

This compound (5, 10, 20 mg/kg); FK866 (HY-50876) (10 mg/kg); SHP099 (HY-100388) (20 mg/kg); FK866 + SHP099 (10 + 20 mg/kg)
Administration:

This compound and SHP099: Oral gavage (p.o.); FK866: Intraperitoneal injection (i.p.); once daily (q.d.) for 15 days
Result:

Dose-dependently suppressed tumor growth with TGI values of 38% (5 mg/kg), 50% (10 mg/kg), and 68% (20 mg/kg), surpassing the efficacy of FK866 (TGI = 19%), SHP099 (TGI = 24%), and the FK866 + SHP099 combination (TGI = 35%).
No significant body weight loss was observed in any treatment group throughout the dosing period.
H&E staining of excised tumor tissues revealed nuclear retraction and reduced tumor cellularity.
H&E staining of major organs (heart, liver, spleen, lung, kidney) showed no significant histological changes between the control and experimental groups, indicating favorable biosafety.

Animal Model:

Female BALB/c nude mice (6-8 weeks old) or immunocompetent female BALB/c mice were inoculated subcutaneously in the right flank with 5 × 10⁵ 4T1 cells.^[1]
Dosage:

This compound (10 mg/kg); anti-PD-1 antibody ((HY-P99144)) (5 mg/kg); This compound + anti-PD-1 antibody (10 + 5 mg/kg)
Administration:

This compound: Oral gavage (p.o.), once daily (q.d.) for 15 days; anti-PD-1 antibody: Intraperitoneal injection (i.p.), biweekly (BIW) for 15 days
Result:

Monotherapy suppressed tumor growth with a TGI of 39%, comparable to anti-PD-1 antibody monotherapy (TGI = 40%).
The combination of this compound and anti-PD-1 antibody exhibited superior antitumor efficacy with a TGI of 71%, significantly greater than either monotherapy.
Immunohistochemistry (IHC) staining of tumor tissues revealed a marked increase in CD8⁺ cytotoxic T-cell infiltration in the monotherapy and combination groups, indicating the induction of in vivo antitumor immunity and synergy with PD-1 blockade.
No significant body weight loss was observed in any group.

Chemical Information

Masse moléculaire 496.03
Formule C₂₄H₂₆ClN₇OS
SMILES

NC(CC1)(C)CCN1C(C=N2)=NC(N)=C2SC3=CC=CC(NC(/C=C/C4=CN=CC=C4)=O)=C3Cl
Livraison

Room temperature in continental US; may vary elsewhere.
Stockage

Please store the product under the recommended conditions in the Certificate of Analysis.

Pureté et documentation

Instruction de manipulation (2659 KB)

Références

[1]. Wang K, et al. Discovery of Novel Dual Small-Molecule Inhibitors Targeting SHP2 and NAMPT for Overcoming Resistance to Allosteric SHP2 Inhibition. J Med Chem. 2026 Jun 22. [Content Brief]

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How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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