SRX-3207 (SRX3207) is a novel, potent, orally bioactive and dual inhibitor of Syk-PI3K with anti-tumor activity. As a first-in-class' dual Syk/PI3K inhibitor, SRX3207 was designed for the combinatorial inhibition of Syk and PI3K in one small molecule. This chemotype demonstrates efficacy in multiple tumor models and represents a novel combinatorial approach to activate antitumor immunity.

Physicochemical Properties

Molecular Formula	C29H29N7O3S
Molecular Weight	555.6507
Exact Mass	555.21
Elemental Analysis	C, 62.69; H, 5.26; N, 17.65; O, 8.64; S, 5.77
CAS #	2254693-15-5
Related CAS #	2254693-15-5;
PubChem CID	137357450
Appearance	Light yellow to light brown solid powder
LogP	4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	7
Heavy Atom Count	40
Complexity	923
Defined Atom Stereocenter Count	0
InChi Key	ZZVOPDBZUNUMPR-UHFFFAOYSA-N
InChi Code	InChI=1S/C29H29N7O3S/c1-19-21(16-34-9-2-10-34)17-36(33-19)25-7-8-30-29(32-25)31-22-5-3-20(4-6-22)23-18-40-28-24(37)15-26(39-27(23)28)35-11-13-38-14-12-35/h3-8,15,17-18H,2,9-14,16H2,1H3,(H,30,31,32)
Chemical Name	3-[4-[[4-[4-(1-Azetidinylmethyl)-3-methyl-1H-pyrazol-1-yl]-2-pyrimidinyl]amino]phenyl]-5-(4-morpholinyl)-7H-thieno[3,2-b]pyran-7-one
Synonyms	SRX-3207 SRX3207 SRX 3207
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

ln Vitro	At concentration, SRX3207 (10 μmol/L) can block p-AKT[1]. The solubility of SRX3207 in water is adequate, at 43 μmol/L [1].
ln Vivo	SRX3207 (10 mg/kg, orally) enhances anticancer immune response[1].
Animal Protocol	Animal/Disease Models: LLC or B16 or B16-OVA or CT26 (1 × 105) cells were injected subcutaneously (sc) into syngeneic mice[1]. Doses: 10 mg/ kg. Route of Administration: Orally, starting from day 10 when tumors reached 100 mm3 until tumors were harvested on day 21. Experimental Results: Blocked phosphorylation of Syk at 348 site and Y525/526 site. Blocked immunosuppressive MΦ polarization. Blocked tumor growth and increased survival effectively .
References	[1]. Macrophage Syk–PI3Kγ Inhibits Antitumor Immunity: SRX3207, a Novel Dual Syk–PI3K Inhibitory Chemotype Relieves Tumor Immunosuppression. Molecular Cancer Therapeutics. 2020. [2]. Macrophage Syk-PI3Kγ Inhibits Antitumor Immunity: SRX3207, a Novel Dual Syk-PI3K Inhibitory Chemotype Relieves Tumor Immunosuppression. Mol Cancer Ther. 2020 Mar;19(3):755-764.

Solubility Data

Solubility (In Vitro)

DMSO : ~5 mg/mL (~9.00 mM)

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	1.7997 mL	8.9985 mL	17.9969 mL
	5 mM	0.3599 mL	1.7997 mL	3.5994 mL
	10 mM	0.1800 mL	0.8998 mL	1.7997 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.