PF-07284892 (ARRY-558) is a potent orally bioactive SHP2 inhibitor (antagonist) with IC50 of 21 nM. PF-07284892 reduces pERK expression.

Physicochemical Properties

Molecular Formula	C21H22CLN7S
Molecular Weight	439.964280605316
Exact Mass	439.134
CAS #	2498597-94-5
PubChem CID	155164064
Appearance	White to off-white solid powder
LogP	2.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	3
Heavy Atom Count	30
Complexity	590
Defined Atom Stereocenter Count	1
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
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
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	IC50: 21 nM (SHP2)[1]
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].
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].
References	[1]. Ongoing progress in BRAF-mutated non-small cell lung cancer. Clin Adv Hematol Oncol. 2022 Nov;20(11):662-672. [2]. SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy. Cancer Discov. 2023 Jun 3:OF1-OF13.
Additional Infomation	SHP2 Inhibitor PF-07284892 is a small molecule inhibitor of protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; Src homology region 2 domain phosphatase; PTPN11), with potential antineoplastic activity. Upon administration, SHP2 inhibitor PF-07284892 targets, binds to and inhibits the activity of SHP2. This prevents SHP2-mediated signaling, inhibits MAPK signaling and prevents growth of SHP2-expressing tumor cells. SHP2, an oncoprotein overexpressed in a variety of cancer cell types, regulates cell survival, differentiation and proliferation through activation of the Ras-Raf-MEK-ERK signaling pathway. The Ras-MAPK pathway is often hyperactivated in cancer cells due to specific mutations and rearrangements, and are dependent on SHP2 for their oncogenic signaling. SHP2 also regulates programmed cell death 1 (PD-1)-mediated signal transduction and is involved in immune checkpoint modulation.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.