rs4;11

MD-224是一种基于蛋白水解靶向嵌合体（PROTAC）概念的高效、高效的MDM2降解剂，是一类新型抗癌剂。

USP7-IN-4(USP7 inhibitor ALM4)是一种非竞争性、高效、选择性的 USP7（泛素特异性蛋白酶7）抑制剂， IC50=6 nM，上调p53和p21，下调MDM2，增加MDM2 的泛素化水平，在多种癌细胞系中表现出抗增殖活性，RS4;11（急性淋巴细胞白血病细胞系）中EC50 = 2.0 nM。

PROTAC BET degrader-2 is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins, with an IC50 of 9.6 nM.

Lenalidomide-C4-NH2 hydrochloride is a Cereblon ligand derived from Lenalidomide. It serves as a recruiting agent for the CRBN protein. The compound, known as PROTAC (Compound 24), can be formed by linking Lenalidomide-C4-NH2 hydrochloride to the ligand for the protein. It exhibits inhibitory effects with IC50s of 0.98 nM and 13.7 nM against the growth of RS4;11 and MOLM-13 acute leukemia cell lines, respectively[1].

KT-253 是一种 p53 稳定剂和 MDM2 的 PROTAC 降解剂 (DC50=0.4 nM)。它可以抑制癌细胞 RS4;11 的增殖 (IC50为 0.3 nM)，导致细胞在 G2 M 期停滞，并诱导细胞凋亡 (apoptosis)。此外，KT-253 在小鼠模型中显示出显著的抗肿瘤活性。(Pink: ligand for target proteinMDM2ligand 4; Black: linker; Blue: ligand for E3 ligasecereblon)

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.

USP7-IN-9是一种高效USP7抑制剂，其IC50值为40.8 nM。该化合物可诱导RS4; 11 细胞发生(apoptosis)，并使细胞周期在G0 G1及S期停滞。此外，USP7-IN-9能够降低癌症相关蛋白MDM2和DNMT1的表达量，同时增加抑癌蛋白p53与p21的表达量。

Bcl-2-IN-4 是一种有效的、具有口服活性的选择性Bcl-2抑制剂，IC50为 1.5 nM。Bcl-2-IN-4 的选择性比Bcl-xL 高于 200 倍 (IC50为 411 nM)。Bcl-2-IN-4 抑制 RS4； 11 细胞增殖，IC50为 2.7 nM。

Bcl-2-IN-5 是一种BCL-2抑制剂，对Bcl-2野生型、Bcl-2D103Y 和Bcl-2G101V 的IC50分别为 0.12 nM、0.14 nM 和 0.22 nM。Bcl-2-IN-5 抑制细胞生长，对 Bcl 2-G101V 敲入RS4; 11 和 RS4; 11 细胞的IC50值分别 0.2 nM 和 0.44 nM。

U7D-1 是一种首创的、有效的和选择性的泛素特异性蛋白酶 7USP7PROTAC 降解剂，在 RS4;11 细胞中DC50为 33 nM。U7D-1 具有抗癌活性。U7D-1 可诱导 Jeko-1 细胞凋亡 (apoptosis)。

AD4是一种青蒿素衍生的PROTACs，具有针对PCLAF的高效降解能力，在RS4;11细胞中的IC50仅为0.6 nM。通过激活p21 Rb轴，AD4展现出明显的抗肿瘤活性。此外，AD4在NOD SCID小鼠移植的RS4;11模型中显著延长了生存时间，证实了其体内疗效。

XM-U-14 是一种高效的PROTAC USP7降解剂,通过诱导RS4;11细胞系中USP7的降解(DC50为0.74 nM)而发挥作用.该化合物能显著提升p53和p21的表达水平,并且有效抑制急性淋巴细胞白血病(ALL)细胞的生长,其IC50值在RS4;11和Reh细胞中分别为0.5 nM和8.3 nM.此外,XM-U-14还能诱导细胞凋亡和周期停滞,有效抑制肿瘤生长.