AS-99 TFA is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity. AS-99 TFA blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1]. AS-99 TFA is tested against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. NO significant inhibition is observed at 50 μM of AS-99 TFA on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L[1].AS-99 TFA shows effect on the growth of the MLL leukemia cells (MV4;11, MOLM13, KOPN8, RS4;11) with the GI50 values ranging from 1.8 μM to 3.6 μM[1].AS-99 (1-8 μM; 7 days) TFA also induces apoptosis in the MLL leukemia cells, but not in the K562 cells, as assessed by the quantification of the Annexin V positive cells[1].AS-99 TFA suppresses MLL fusion driven transcriptional programs[1]. AS-99 (30 mg kg; i.p.; q.d., treated for 14 consecutive days) TFA reduces leukemia burden in mice[1].AS-99 TFA is used for in vivo studies in mice, which reveals favorable exposure in plasma upon i.v. and i.p. administration (AUC = 9701 hr* ng mL and 10,699 hr* ng mL, respectively), suitable half-life (~5-6 h) and Cmax >10 μM[1]. [1]. David S. Rogawski, Jing Deng, Hao Li, Tomasz Cierpicki, Jolanta Grembecka, et al. Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity. Nat Commun. 2021 May 14;12(1):2792.
MIPS-9922 is a potent and selective PI3Kβ inhibitor with antiplatelet activity. MIPS-9922 inhibited integrin αIIbβ3 activation and αIIbβ3 dependent platelet adhesion to immobilized vWF under high shear. MIPS-9922 also potently inhibited ADP-induced washe
L6H9 is a novel inhibitor of myeloid differentiation factor 2 (MD2), suppressing HG-induced expression of ACE and AT1 receptor and Angiotensin II (AngII) production in renal NRK‐52E cells, resulting in the decrease in fibrosis markers such as TGF-β and collagen IV.
Rugulotrosin A is an antibiotic originally isolated from Penicillium. It is active against the Gram-positive bacteria E. faecalis, B. cereus, B. subtilis, and S. aureus with 99% lethal dose (LD99) values of 1.6, 3.1, 5.5, and 200 μg ml, respectively. Rugulotrosin A is inactive against Gram-negative bacteria.