RK-701

• CAT Number: I041951
• CAS Number: 2648855-18-7
• Molecular Formula: C26H30N4O3
• Molecular Weight: 446.54
• Purity: ≥95%
• Synonyms: N-[(2S)-1-(4-cyanoanilino)-4-cyclopropyl-1-oxobutan-2-yl]-3,6,6-trimethyl-4-oxo-5,7-dihydro-1H-indole-2-carboxamide
• InChI: InChI=1S/C26H30N4O3/c1-15-22-20(12-26(2,3)13-21(22)31)29-23(15)25(33)30-19(11-8-16-4-5-16)24(32)28-18-9-6-17(14-27)7-10-18/h6-7,9-10,16,19,29H,4-5,8,11-13H2,1-3H3,(H,28,32)(H,30,33)/t19-/m0/s1
• InChIKey: OWORSODZTADOQX-IBGZPJMESA-N
• SMILES: CC1=C(NC2=C1C(=O)CC(C2)(C)C)C(=O)NC(CCC3CC3)C(=O)NC4=CC=C(C=C4)C#N

RK-701 is an highly selective and non-genotoxic inhibitor of G9a with IC50 value of 23-27 nM. RK-701 selectively up-regulates HbF, γ- Globin, BGLT3 expression, down-regulates H3K9me2 expression. RK-701 also has inhibition for BCL11A and ZBTB7A[1].
RK-701 (0.01-3 µM; 4 d) up-regulates the expression level of HbF and γ-globin mRNA without affecting cell viability or erythroid differentiation. RK-701 increases the proportion of HbF expressing cells in a concentration-dependent manner. In HUDEP-2 cells and human primary CD34+ cells, RK-701 also selectively up-regulates the expression level of BGLT3 and reduces the proportion of H3K9me2 in β-globin[1].
RK-701 (1 µM; 4 d) significantly reduces the proportion of BCL11A and ZBTB7A in BGLT3 without increasing the expression of BGLT3 in HUDEP-2 cells under the absence of BCL11A or ZBTB7A[1].
RK-701 (20 mg/kg and 50 mg/kg; i.p.; 5 weeks, each week for 5 consecutive days) selectively increases mouse embryos ε Y-globin and significantly down-regulates the expression level of H3K9me2 in peripheral blood cells. RK-701 has low toxicity[1].

Reference

[1]. Takase S, et al. A specific G9a inhibitor unveils BGLT3 lncRNA as a universal mediator of chemically induced fetal globin gene expression. Nat Commun. 2023 Jan 12;14(1):23.
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