ASN007 (ASN-007) is a novel, potent, orally bioavailable and selective inhibitor of ERK1/2 with robust antitumor activity. It blocks ERK1/2 with an IC50 of 2 nM and the RAS/RAF/MEK/ERK (MAPK) signaling pathway. Regardless of the mutation's subtype, ASN007 exhibits strong preclinical activity in KRAS-driven models as well as BRAF mutant models, including melanoma resistant to RAF/MEK inhibitors.

Physicochemical Properties

Molecular Formula	C22H25CLFN7O2
Molecular Weight	473.931006193161
Exact Mass	473.17
Elemental Analysis	C, 55.75; H, 5.32; Cl, 7.48; F, 4.01; N, 20.69; O, 6.75
CAS #	2055597-12-9
Related CAS #	ASN007 benzenesulfonate;2055597-39-0
PubChem CID	124122366
Appearance	White to light yellow solid powder
LogP	2.3
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	644
Defined Atom Stereocenter Count	1
SMILES	CC1=CN=C(N=C1N2C=C(N=C2)C(=O)N[C@H](CN)C3=CC(=CC(=C3)Cl)F)NC4CCOCC4
InChi Key	PWHIUQBBGPGFFV-GOSISDBHSA-N
InChi Code	InChI=1S/C22H25ClFN7O2/c1-13-10-26-22(28-17-2-4-33-5-3-17)30-20(13)31-11-19(27-12-31)21(32)29-18(9-25)14-6-15(23)8-16(24)7-14/h6-8,10-12,17-18H,2-5,9,25H2,1H3,(H,29,32)(H,26,28,30)/t18-/m1/s1
Chemical Name	N-[(1S)-2-amino-1-(3-chloro-5-fluorophenyl)ethyl]-1-[5-methyl-2-(oxan-4-ylamino)pyrimidin-4-yl]imidazole-4-carboxamide;benzenesulfonic acid
Synonyms	ASN007; ASN 007; ASN-007
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	ERK1; ERK2
ln Vitro	In various cell lines, ERK-IN-3 prevents the phosphorylation of ERK1/2 substrates like RSK1, FRA1, and Elk1[1]. Single-digit nanomolar antiproliferative activity of ERK-IN-3 is specific for cancer cell lines that are MAPK pathway dependent[1].
ln Vivo	At effective doses, ERK-IN-3 (daily p.o.) was well tolerated and inhibited tumor growth in several BRAF and KRAS mutant mouse xenograft models[1].
References	[1]. Abstract B150: ASN007, a novel oral ERK inhibitor, shows robust antitumor activity in RAS mutant cancer models. Molecular Cancer Therapeutics. 2018 Jan; 17(1).
Additional Infomation	ERK1/2 Inhibitor ERAS-007 is an orally bioavailable inhibitor of the extracellular signal-regulated kinases 1 (ERK1) and 2 (ERK2), with potential antineoplastic activity. Upon oral administration, ERAS-007 specifically binds to and inhibits the serine/threonine-protein kinase activities of both ERK1 and ERK2, thereby preventing the phosphorylation of ERK1/2 substrates and the activation of mitogen-activated protein kinase (MAPK)/ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent proliferation and survival of tumor cells. The MAPK/ERK pathway, also known as the RAS/RAF/MEK/ERK pathway, is hyperactivated in a variety of tumor cell types due to mutations in upstream targets. It plays a key role in the proliferation, differentiation and survival of tumor cells.

Solubility Data

Solubility (In Vitro)

DMSO: 95 ~200 mg/mL (200.5~422 mM) Ethanol: ~95 mg/mL (~200.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 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 3: ≥ 2.08 mg/mL (4.39 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 6.67 mg/mL (14.07 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1100 mL	10.5501 mL	21.1002 mL
	5 mM	0.4220 mL	2.1100 mL	4.2200 mL
	10 mM	0.2110 mL	1.0550 mL	2.1100 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.