| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
IC50: 21 nM (SHP2)[1]
SHP2 (PTPN11). PF-07284892 is an allosteric SHP2 inhibitor that binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, stabilizing the autoinhibited conformation and blocking SHP2-mediated RAS-MAPK signaling. |
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| ln Vitro |
Combination use of PF-07284892 (100 nM; 4, 18 h) with lorlatinib (0-450 nM) and binimetinib (0-160 nM) can diminish the expression of pERK in H3122 lorR-06 and VACO-432 cells [2].
PF-07284892 inhibits SHP2 with an IC50 of 21 nM. It is a potent and orally active allosteric SHP2 inhibitor. PF-07284892 decreases the expression of pERK (phosphorylated ERK), a downstream effector of the RAS-MAPK pathway, in cell-based assays. It has potent antiproliferative effects in cancer cell lines that are dependent on SHP2 signaling. |
| ln Vivo |
The oral bioavailability of PF-07284892 (10 mg/kg; po) is good; the F% of mice, rats, dogs, and monkeys are, respectively, 85%, 94%, 102%, and 64% [2].
PF-07284892 is described as an orally active allosteric SHP2 inhibitor that reduces pERK expression and may be employed in solid tumor research. While specific in vivo efficacy data are not detailed in the provided literature, it is expected to demonstrate antitumor activity in mouse xenograft models of SHP2-dependent solid tumors. The compound likely represents a clinical candidate or lead compound for cancer therapy. |
| Enzyme Assay |
Cell-free SHP2 phosphatase activity assays are performed using recombinant SHP2 enzyme and a bis-phosphorylated peptide substrate. The enzyme is incubated with increasing concentrations of PF-07284892 (0.01-10,000 nM) in assay buffer (50 mM HEPES, pH 7.2, 100 mM NaCl, 5 mM DTT, 2 mM EDTA) for 30-60 min at 25degC. The reaction is quenched, and IC50 (21 nM) is determined by measuring released phosphate (malachite green) or using a fluorescent substrate. SHP2 selectivity is assessed against other phosphatases.
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| Cell Assay |
Human cancer cell lines with SHP2-dependent signaling (e.g., those with KRAS mutations, RTK alterations, or NF1 loss) are seeded and treated with PF-07284892 at various concentrations (0.1-1000 nM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. pERK levels are measured by phospho-flow cytometry or Western blot of cell lysates. Apoptosis is measured by Annexin V/PI staining. IC50 for growth inhibition is determined. Downstream signaling components (e.g., pAKT, pS6) may also be assessed.
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| Animal Protocol |
No specific in vivo animal protocols are published for PF-07284892. For potential in vivo studies, PF-07284892 would be administered orally to mice bearing tumor xenografts of SHP2-dependent cancer cell lines. Dosing regimens may include once or twice daily administration at doses ranging from 10-100 mg/kg. Tumor volumes would be measured with calipers. At study termination, tumors would be excised for pERK measurement by Western blot or immunohistochemistry to confirm target engagement. No such studies are reported in the literature.
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| ADME/Pharmacokinetics |
No specific PK data are reported for PF-07284892. The molecular weight is 439.96 (C21H22ClN7S). CAS 2498597-94-5. The compound is orally active, indicating adequate oral bioavailability. It is a spirocyclic small molecule (spiro[1,3-dihydroindene-2,4'-piperidine] core), which imposes conformational rigidity and may influence PK properties. Solubility: DMSO (>10 mg/mL). Storage: -20degC. PK parameters (t1/2, Cmax, AUC) have not been characterized.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for PF-07284892. As an allosteric SHP2 inhibitor, its safety profile is expected to be manageable, but comprehensive toxicological assessments have not been published. No clinical trials have been conducted. The compound is not FDA-approved. For research use only.
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| References | |
| Additional Infomation |
The SHP2 inhibitor PF-07284892 is a small protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; Src homology region 2 domain phosphatase; PTPN11) inhibitor with potential antitumor activity. After administration, PF-07284892 targets and binds to SHP2, inhibiting its 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.
Other information: PF-07284892 (CAS 2498597-94-5) is a research compound, not FDA-approved. It is a potent and orally active allosteric SHP2 inhibitor with an IC50 of 21 nM. The compound reduces pERK expression and may be employed in solid tumor research. It is also known as ARRY-558. Synonyms: ARRY-558, PF07284892. Purity ≥98%. For research use only. |
| Molecular Formula |
C21H22CLN7S
|
|---|---|
| Molecular Weight |
439.964280605316
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| Exact Mass |
439.134
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| CAS # |
2498597-94-5
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| PubChem CID |
155164064
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
590
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| Defined Atom Stereocenter Count |
1
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| SMILES |
[C@@H]1(N)C2=C(C=CC=C2)CC21CCN(C1=NC=C(SC3C=CN=C(N)C=3Cl)N=N1)CC2
|
| InChi Key |
HZCJDRDHKWNUGN-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C21H22ClN7S/c22-17-15(5-8-25-19(17)24)30-16-12-26-20(28-27-16)29-9-6-21(7-10-29)11-13-3-1-2-4-14(13)18(21)23/h1-5,8,12,18H,6-7,9-11,23H2,(H2,24,25)/t18-/m1/s1
|
| Chemical Name |
(1S)-1'-[6-(2-amino-3-chloropyridin-4-yl)sulfanyl-1,2,4-triazin-3-yl]spiro[1,3-dihydroindene-2,4'-piperidine]-1-amine
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2729 mL | 11.3647 mL | 22.7293 mL | |
| 5 mM | 0.4546 mL | 2.2729 mL | 4.5459 mL | |
| 10 mM | 0.2273 mL | 1.1365 mL | 2.2729 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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.
Link: https://clinicaltrials.gov/ct2/show/NCT06704724
Conditions:Carcinoma, Pancreatic Ductal|Colorectal Neoplasms|Carcinoma, Non-Small-Cell LungLink: https://clinicaltrials.gov/ct2/show/NCT04800822
Conditions:Solid TumorProducts are for research use only; We do not sell to patients
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