tumor suppression

KW-2450 free base 是一种 IGF-1R IR和酪氨酸激酶多重抑制剂 具有抗肿瘤活性。KW-2450 free base 在小鼠 HT-29 GFP 结肠癌异种移植模型中显示出适度的生长抑制活性并抑制 IGF-1 诱导的信号转导。

Halofuginone hydrobromid 是Febrifugine 的衍生物，是竞争性脯氨酰-tRNA 合成酶抑制剂。它是 I 型胶原合成的特异性抑制剂，并通过抑制TGF-β活性可减轻骨关节炎。它具有抗疟疾、抗炎、抗癌、抗纤维化作用。

RMC-6291 是一种可口服且具有高效性的 KRASG12C(ON) 抑制剂，具有抗癌抗肿瘤活性，通过空间阻断 RAS 效应子结合来发挥作用。RMC-6291 阻断 ERK 信号传导，促使 KRASG12C 突变 H358 细胞凋亡。

Cyproterone acetate (Cyproterone 17-O-acetate) 是能够抗雄激素(IC50=7.1 nM) 和孕激素合成的类固醇。它与 progesteron 和糖皮质激素受体有亲和力。

XRK3F2 是 p62-ZZ 结构域的抑制剂，在体外减弱 MM 诱导的 Runx2 抑制，在体内肿瘤存在的情况下诱导新骨形成和重塑。

SKLB646 是一种口服多靶点激酶抑制剂，其抑制效果针对多种激酶。在对SRC和VEGFR2的抑制上，SKLB646表现出强效性，其IC50分别为0.002 μmol L和0.012 μmol L。此外，该化合物对B-Raf 和 C-Raf的抑制IC50分别为0.022 μmol L和0.019 μmol L。SKLB646能有效抑制SRC信号通路的激活，并阻断MAPK信号通路，通过抑制Raf激酶达到这种效果。SKLB646亦可阻止人脐静脉内皮细胞（HUVEC）的增殖、迁移和侵袭，并抑制肿瘤诱导的心血管生成。对于三阴性乳腺癌（TNBC）细胞系，SKLB646显示了显著的抗增殖和抗生存活性。

FL442作为一种Androgen Receptor(AR) 调节剂，在AR依赖性前列腺癌细胞中展现出显著的抑制活性，其效率与Bicalutamide和Enzalutamide这类传统抗雄激素药物相似。此外，FL442针对于对Enzalutamide显示较强耐药性的AR突变体F876L也保持了抗雄激素活性。在小鼠模型中，FL442的药代动力学特征表明该化合物具有较长的半衰期（8小时）、针对前列腺组织的良好定向性及优异的代谢稳定性，且在低血浆浓度（30 ng mL）下依然能有效抑制LNCaP肿瘤生长。

PF-07265028 是一种HPK1抑制剂，其IC50为17 nM。在进行了体内药代动力学研究后，PF-07265028在小鼠和猴子体内表现出适中的清除率、终端半衰期、分布容积及口服生物利用度。PF-07265028定位、结合并抑制Hpk1的活性，进而阻断Hpk1介导的信号传导途径，防止Hpk1介导的免疫抑制，包括阻止T细胞受体（TCR）信号的抑制、效应T细胞的抑制、破坏异常的细胞因子表达，并消除免疫抑制性肿瘤微环境（TME）。这可能激活针对肿瘤细胞的细胞毒性T淋巴细胞（CTL）介导的免疫反应。Hpk1主要在造血细胞中表达，是TCR信号和T、B细胞激活的负向调节因子。

N-Ethyl-N-nitrosourea (ENU) 是一种 DNA 烷基化剂。通过烷基化核碱基，N-Ethyl-N-nitrosourea 损害 DNA，导致骨髓抑制及白血病细胞生成，从而诱发白血病。其在体内具有致畸性，可使怀孕大鼠形成肿瘤和产生足部畸形。此外，N-Ethyl-N-nitrosourea 还会引起中枢神经系统 (CNS) 肿瘤及遗传性疾病。

Ferroptosis-IN-17 (Compound 18) 是一种铁死亡抑制剂，EC50值为0.57 μM。它能够减少细胞内亚铁离子积累和脂质过氧化，同时有效恢复谷胱甘肽 (GSH) 和谷胱甘肽过氧化物酶 4 (GPX4) 水平。在大鼠血浆中，Ferroptosis-IN-17 显示出良好的溶解度和显著的代谢稳定性。该化合物在肿瘤抑制、神经退行性疾病以及心血管疾病的研究中展现出潜力。

CYCS-INPP4A interaction-IN-1 (10A3) 通过破坏CYCS-INPP4A相互作用复合物，有效增强了铁死亡介导的肿瘤抑制。

PD-L1inhibitory peptide是一种靶向程序性细胞死亡配体1 (PD-L1) 的抑制剂肽。它通过结合PD-L1解除免疫抑制，恢复T细胞的抗肿瘤活性， 并有望应用于肿瘤研究。

Cytochalasin D is an actin inhibitor, the removal of actin stress fibers is crucial for the chondrogenic differentiation. It may be an inhibitor of some fertilization processes such as sperm penetration or sperm head decondensation. Cytochalasin D inhibit

TAS-103 is a dual inhibitor of DNA topoisomerase I II, used for cancer research. TAS-103 is a dual inhibitor of DNA topoisomerase I II. TAS-103 (0.1-10 μM) is active on CCRF-CEM cells, with an IC50 value of 5 nM. TAS-103 (0.1 μM) significantly increases levels of topo IIα FITC immunofluorescence in individual CCRF-CEM cells[1]. TAS-103 (0.01-1 μM) is highly cytotoxic to Lewis lung carcinoma (LLC) cells, and Liposomal TAS-103 is almost as active as free TAS-103[2]. TAS-103 inhibits the viability of HeLa cells, with an IC50 of 40 nM. TAS-103 (10 μM) disrupts signal recognition particle (SRP) complex formation, and induces destabilization of SRP14 and SRP19 and its eventual degradation[3]. TAS-103 (30 mg kg, i.v.) causes significant tumor growth suppression in mice bearing Lewis lung carcinoma (LLC) cells, without obvious body weight loss, and the liposomal TAS-103 is more active than free TAS-103[2]. [1]. Padget K, et al. An investigation into the formation of N- [2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) and 6-[2-(dimethylamino)ethylamino]- 3-hydroxy-7H-indeno[2, 1-C]quinolin-7-one dihydrochloride (TAS-103) stabilised DNA topoisomerase I and II cleavable complexes in human leukaemia cells. Biochem Pharmacol. 2000 Sep 15;60(6):817-21. [2]. Shimizu K, et al. Cancer chemotherapy by liposomal 6-[12-(dimethylamino)ethyl]aminol-3-hydroxy-7H-indeno[2,1-clquinolin-7-one dihydrochloride (TAS-103), a novel anti-cancer agent. Biol Pharm Bull. 2002 Oct;25(10):1385-7. [3]. Yoshida M, et al. A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads. Mol Pharmacol. 2008 Mar;73(3):987-94. Epub 2007 Dec 18.

Picropodophyllotoxin (AXL 1717) 是一种环木脂素生物碱，存在于五月树(Podophyllum peltatum) 中，是一种具有潜在抗肿瘤活性的胰岛素样生长因子 1 受体 (IGF1R) 的小分子抑制剂。它特异性抑制 IGF1R 的活性并下调细胞表达，而不干扰其他生长因子受体的活性，例如胰岛素受体、表皮生长因子、血小板衍生生长因子、成纤维细胞生长因子和肥大 干细胞生长因子 (KIT) ）。该药剂在抑制肿瘤细胞增殖和诱导肿瘤细胞凋亡方面显示出有效的活性。 IGF1R 是一种在多种人类癌症中过度表达的受体酪氨酸激酶，在多种癌细胞的生长和存活中起关键作用。

Anticancer agent 68 is (Compound 12) 是一种抗癌剂。Anticancer agent 68 将细胞阻滞在 G2 M 期并诱导程序性细胞死亡。Anticancer agent 68 通过激活 p53 和 PTEN 诱导上调肿瘤抑制。

CD73-IN-12 is a highly effective CD73 inhibitor that displays strong potential in tumor suppression. CD73, an enzyme intricately linked to tumor development, angiogenesis, and metastasis, is significantly inhibited by CD73-IN-12. This compound holds promise in the formulation of therapeutic medications targeting tumor-related diseases[1].

R-130823 is a ighly selective inhibition against mitogen-activated protein kinase p38alpha (IC50=22 nM). The release of tumor necrosis factor-alpha, interleukin-1beta, -6 and -8 was inhibited in lipopolysaccharide-stimulated human blood pretreated by R-130823 , with IC50 values of 0.089, 0.066, 0.95 and 0.16 microM, respectively. R-130823 reduced the established hind paw swelling in rat adjuvant-induced arthritis, while methotrexate showed no suppression. In the same model, R-130823 ameliorated adjuvant-induced hyperalgesia with rapid onset and long duration comparable to a cyclooxygenase-2 inhibitor, celecoxib.

KW-2450 Tosylate is an orally bioavailable inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) tyrosine kinases with potential antineoplastic activity. IGF-1R IR inhibitor KW-2450 Tosylate selectively binds to and inhibits the activities of IGF-1R and IR, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-R1 and IR tyrosine kinases, overexpressed in a variety of human cancers, play significant roles in the stimulation of cellular proliferation, oncogenic transformation, and suppression of apoptosis.

CB-1158-analog, also known as Numidargistat-analog and INCB01158-analog, is a potent and orally active arginase inhibitor with IC50=89 nM) . CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. CB-1158 may be potentially useful in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. (see ADDITIONAL INFORMATION in this web page for CB-1158 structure confusion).

Patidegip, laos known as Saridegib and IPI-926, is an orally bioavailable, cyclopamine-derived (for structure comparison see Fig 1) inhibitor of the Hedgehog (Hh) pathway with potential antineoplastic activity. Specifically, Hedgehog pathway inhibitor IPI-926 binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. SMO is activated upon binding of Hh ligand to the cell surface receptor Patched (PTCH); inappropriate activation of Hh signaling and uncontrolled cellular proliferation may be associated with SMO mutations.

LEQ506, also known as NPV-LEQ506, is an orally bioavailable small-molecule Smoothened (Smo) antagonist with potential antineoplastic activity. Smoothened antagonist LEQ506 selectively binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway, thereby inhibiting tumor cell growth.

CPT-Se4为含硒前体活性分子的喜树碱(CPT)衍生物，对癌细胞具有较高杀伤力和抑制肿瘤生长效果。在降低GSH GSSG比率和总硫醇的同时，CPT-Se4能够增加Hep G2细胞中的ROS水平，触发癌细胞凋亡。此化合物对HeLa、Hep G2、A549和SMMC-7721细胞系显示出显著的细胞毒性，IC50值范围为2.54-6.4 μM。

PROTACBTK Degrader-1 是一种有效且具有选择性和口服活性的PROTACBTK 降解剂，对野生型BTK 和突变型 BTK-481S 的IC50分别为 34.51 nM 和 64.56 nM。PROTACBTK Degrader-1 能有效降低BTK 蛋白水平，抑制肿瘤生长。