Synonym
SPI-112; SPI112; SPI 112.
IUPAC/Chemical Name
(Z)-3-(2-(5-(N-(4-Fluorobenzyl)sulfamoyl)-2-oxoindolin-3-ylidene)hydrazinyl)benzoic acid
InChi Key
ABVSYWGFUNXYAC-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H17FN4O5S/c23-15-6-4-13(5-7-15)12-24-33(31,32)17-8-9-19-18(11-17)20(21(28)25-19)27-26-16-3-1-2-14(10-16)22(29)30/h1-11,24,26H,12H2,(H,29,30)(H,25,27,28)
SMILES Code
O=C(O)C1=CC=CC(N/N=C2C(NC3=C\2C=C(S(=O)(NCC4=CC=C(F)C=C4)=O)C=C3)=O)=C1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO and DMF
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
SPI-112 inhibits SHP-2 in cell-free assays (IC50 = 1 µM). SPI-112 selectively inhibits SHP-2 over SHP-1 and protein tyrosine phosphatase 1B (PTP1B; IC50s = 18.3 and 14.5 µM, respectively).
In vitro activity:
SPI-112 binds to Shp2 with competitive inhibitor kinetics but lacked cell permeability, limiting its use in biological studies. This study developed SPI-112Me and found it to be cell permeable and inhibited Shp2 activity, paxillin dephosphorylation, Erk1/2 activation, and cell migration. SPI-112Me also inhibited Shp2(E76K)-dependent cell survival and enhanced interferon-gamma-stimulated signaling. Thus, SPI-112Me effectively inhibited cellular Shp2 activity.
Reference: Biochem Pharmacol. 2010 Sep 15;80(6):801-10. https://pubmed.ncbi.nlm.nih.gov/20510203/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
1.0 |
2.13 |
|
| DMSO |
2.0 |
4.27 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
468.45
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Chen L, Pernazza D, Scott LM, Lawrence HR, Ren Y, Luo Y, Wu X, Sung SS, Guida WC, Sebti SM, Lawrence NJ, Wu J. Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112. Biochem Pharmacol. 2010 Sep 15;80(6):801-10. doi: 10.1016/j.bcp.2010.05.019. Epub 2010 May 25. PMID: 20510203; PMCID: PMC2906681.
In vitro protocol:
1. Chen L, Pernazza D, Scott LM, Lawrence HR, Ren Y, Luo Y, Wu X, Sung SS, Guida WC, Sebti SM, Lawrence NJ, Wu J. Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112. Biochem Pharmacol. 2010 Sep 15;80(6):801-10. doi: 10.1016/j.bcp.2010.05.019. Epub 2010 May 25. PMID: 20510203; PMCID: PMC2906681.
1: Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112.
Chen L, Pernazza D, Scott LM, Lawrence HR, Ren Y, Luo Y, Wu X, Sung SS, Guida WC, Sebti SM, Lawrence NJ, Wu J. Biochem Pharmacol. 2010 Sep 15;80(6):801-10. doi: 10.1016/j.bcp.2010.05.019. Epub 2010 May 25.
2: Ge, Y., Lawrence, H. R., Chen, L., Scott, L. M., Sebti, S. M., Lawrence, N. J., & Wu, J. (2012). Development of potent SHP2 inhibitors for in vivo studies. Cancer Research, 72(8_Supplement), 2912-2912.
