| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| Targets |
SHP2-IN-6 targets SHP2 (encoded by PTPN11), a non-receptor protein tyrosine phosphatase that plays a critical role in the RAS-MAPK signaling pathway. SHP2 is an oncoprotein that is overexpressed in various cancer cell types and regulates cell survival, differentiation, and proliferation by activating the Ras-Raf-MEK-ERK cascade. By allosterically inhibiting SHP2, SHP2-IN-6 prevents the activation of this pathway, thereby suppressing tumor growth.
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|---|---|
| ln Vitro |
SHP2-IN-6（JAB-3068） has an IC50 of 2.17 μM and prevents KYSE-520 cells from proliferating[1].
In vitro, SHP2-IN-6 is a potent SHP2 inhibitor with an IC50 of 25.8 nM. It effectively blocks SHP2-mediated signaling and inhibits the proliferation of SHP2-expressing tumor cells. This compound enhances the anti-tumor activity of CD8+ T-cells, suggesting a role in modulating the tumor immune microenvironment. |
| ln Vivo |
In vivo, SHP2-IN-6 has shown anticancer activity in preclinical models. It has been used in combination with PD-1/PD-L1 antibodies to address non-responsive tumors, indicating its potential to overcome resistance to immunotherapy. Its ability to enhance the anti-tumor activity of immune cells makes it a promising candidate for combination therapy.
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| Enzyme Assay |
The inhibitory activity of SHP2-IN-6 is assessed using in vitro phosphatase assays. Recombinant SHP2 enzyme is incubated with a substrate and varying concentrations of the compound. The dephosphorylation of the substrate is measured, and the IC50 is calculated. Its allosteric mechanism of action is confirmed by its binding to the inactive conformation of the enzyme.
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| Cell Assay |
The cellular activity of SHP2-IN-6 is evaluated in cancer cell lines and primary immune cells. Cells are treated with SHP2-IN-6, and its effect on MAPK signaling is assessed by measuring the phosphorylation of ERK by Western blot. Its effect on cell proliferation, apoptosis, and immune cell function is also investigated.
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| Animal Protocol |
In animal studies, SHP2-IN-6 is typically administered via oral gavage or intraperitoneal (i.p.) injection. In mouse xenograft models, it is given to assess its effect on tumor growth. In combination studies, it is given with PD-1/PD-L1 antibodies to evaluate its ability to enhance anti-tumor immunity.
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| ADME/Pharmacokinetics |
As a small molecule (MW 476.54), SHP2-IN-6 is likely to have oral bioavailability. Its pharmacokinetic properties, such as half-life and exposure, would support once- or twice-daily dosing. Its ability to be used in combination with other agents makes it a valuable tool for preclinical research.
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| Toxicity/Toxicokinetics |
Toxicology data for SHP2-IN-6 is not extensively documented in public sources. As a research compound, its safety profile has not been established in formal toxicology studies. However, its use in animal models suggests it is tolerated at the doses used for efficacy studies.
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| References | |
| Additional Infomation |
JAB-3068, an SHP2 inhibitor, is an orally bioavailable non-receptor 11 protein tyrosine phosphatase (PTP) inhibitor with potential antitumor activity. After oral administration, JAB-3068 targets and inhibits SHP2 activity. This blocks SHP2-mediated signaling, inhibits MAPK signaling, and suppresses the growth of SHP2-expressing tumor cells. SHP2 is an oncoprotein overexpressed in various cancer cell types that regulates cell survival, differentiation, and proliferation by activating the Ras-Raf-MEK-ERK signaling pathway. The Ras-MAPK pathway is typically overactivated in cancer cells due to specific mutations and rearrangements, and its oncogenic signaling is dependent on SHP2. SHP2 also regulates programmed cell death 1 (PD-1)-mediated signaling and is involved in immune checkpoint regulation.
SHP2-IN-6 (JAB-3068, CAS: 2169223-48-5) is a potent and selective allosteric inhibitor of SHP2. It represents a promising therapeutic strategy for targeting the MAPK pathway in cancers that are driven by this signaling cascade. Its ability to enhance the anti-tumor activity of CD8+ T-cells highlights its potential as a combination agent with immunotherapies. It continues to be a key compound for research into SHP2 biology and cancer therapeutics. |
| Molecular Formula |
C22H26F2N6O2S
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|---|---|
| Exact Mass |
476.547
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| Elemental Analysis |
C, 55.45; H, 5.50; F, 7.97; N, 17.64; O, 6.71; S, 6.73
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| CAS # |
2169223-48-5
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| Related CAS # |
JAB-3068 hydrochloride;2169223-49-6
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| PubChem CID |
132222602
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
33
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| Complexity |
740
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(=O)N1CC(C2=C1C=CC=C2SC3=NC=C(N=C3N)N4CCC5(CC4)COC[C@H]5N)(F)F
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| InChi Key |
HGYTYZKWKUXRKA-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C22H26F2N6O2S/c1-13(31)30-11-22(23,24)18-14(30)3-2-4-15(18)33-20-19(26)28-17(9-27-20)29-7-5-21(6-8-29)12-32-10-16(21)25/h2-4,9,16H,5-8,10-12,25H2,1H3,(H2,26,28)/t16-/m1/s1
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| Chemical Name |
1-[4-[3-amino-5-[(4S)-4-amino-2-oxa-8-azaspiro[4.5]decan-8-yl]pyrazin-2-yl]sulfanyl-3,3-difluoro-2H-indol-1-yl]ethanone
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| Synonyms |
SHP2-IN-6; SHP2-IN6; SHP2-IN 6; HMN-23485; HMN 23485; HMN23485
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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