RAS/RAS-RAF-IN-1 is a potent inhibitor of RAS and RAS-RAF. RAS/RAS-RAF-IN-1 has Kd for cyclophilin A (CYPA) binding affinity of 5.0 μM-15 μM. RAS/RAS-RAF-IN-1 displays anti-tumor effects.

Physicochemical Properties

Molecular Formula	C45H57N7O7
Molecular Weight	807.98
Exact Mass	807.431
CAS #	2447039-81-6
PubChem CID	162642485
Appearance	White to light yellow solid powder
LogP	5.2
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	7
Heavy Atom Count	59
Complexity	1660
Defined Atom Stereocenter Count	4
SMILES	C(C1=CN2CC(COC([C@]3([H])CCCN(C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C([C@H]4CCN(C(=O)C=C)C4)=O)CC4C=C(O)C=C(C=4)C4=CC=C1C2=C4)N3)=O)(C)C)(C)(C)C#N
InChi Key	RCXSKUOUWMZVFF-NXCZKTMTSA-N
InChi Code	InChI=1S/C45H57N7O7/c1-9-38(54)50-16-14-30(22-50)41(56)49(8)39(27(2)3)40(55)47-36-19-28-17-31(20-32(53)18-28)29-12-13-33-34(45(6,7)24-46)23-51(37(33)21-29)25-44(4,5)26-59-43(58)35-11-10-15-52(48-35)42(36)57/h9,12-13,17-18,20-21,23,27,30,35-36,39,48,53H,1,10-11,14-16,19,22,25-26H2,2-8H3,(H,47,55)/t30-,35-,36-,39-/m0/s1
Chemical Name	(3S)-N-[(2S)-1-[[(8S,14S)-22-(2-cyanopropan-2-yl)-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,20,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),21,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide
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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	RAS/RAS-RAF-IN-1 (Compound 89) possesses an EC50 of 0.5 μM-5.0 μM for disrupting BRAF-GTP-KRAS-G12C and an IC50 of 1.0 μM-10 μM for inhibiting pERK in H358 cells [1].
References	[1]. Compounds that participate in cooperative binding and uses thereof. WO2020132597A1.

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~247.53 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 6 mg/mL (7.43 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 5 mg/mL (6.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.2377 mL	6.1883 mL	12.3765 mL
	5 mM	0.2475 mL	1.2377 mL	2.4753 mL
	10 mM	0.1238 mL	0.6188 mL	1.2377 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.