CWHM-12是一种强效的αV整合素抑制剂，对αvβ8、αvβ3、αvβ6和αvβ1的IC50值分别为0.2、0.8、1.5和1.8nM。
Cas No.:1564286-55-0
Sample solution is provided at 25 µL, 10mM.
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CWHM-12 is a potent inhibitor of αV integrins with IC50 values of 0.2, 0.8, 1.5, and 1.8nM for αvβ8, αvβ3, αvβ6, and αvβ1[1]. The αV integrin family comprises a group of heterodimeric transmembrane receptors that recognize RGD-containing extracellular matrix proteins and play key roles in mediating cell adhesion, migration, TGF-β activation, and tissue remodeling[2]. CWHM-12 is usually used in research on liver fibrosis, lung fibrosis, and tumor microenvironment[3][4].
In vitro, CWHM-12 (1mM; 3h) completely abolished odontogenesis-associated phosphoprotein (ODAPH)-mediated Tgfb1 upregulation and reversed Alpl expression in mouse ameloblast-lineage cells (ALCs)[5].
In vivo, CWHM-12 (100mg/kg/day; 4 weeks; continuous subcutaneous infusion via mini-osmotic pumps) reversed established liver fibrosis, reduced hepatic collagen content, decreased α-SMA-positive activated hepatic stellate cells, induced HSC apoptosis, and suppressed TGFβ/SMAD3 signaling in a choline deficient, amino-acid defined, high-fat diet (CDAHFD) -induced NASH mouse model[6]. CWHM-12 (100mg/kg/day; 45 days; continuous subcutaneous infusion via mini-osmotic pumps) reduced lung and spleen bacterial burden, decreased alveolar macrophages and neutrophils while increasing recruited macrophages, suppressed iNOS, MIP-2 and IL-10 production, and enhanced collagen deposition in Mycobacterium tuberculosis HN878-infected C3HeB/FeJ mice[7].
References:
[1] Henderson NC, Arnold TD, Katamura Y, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013;19(12):1617-1624.
[2] Lafrenie RM, Yamada KM. Integrin-dependent signal transduction. J Cell Biochem. 1996;61(4):543-553.
[3] Basta J, Robbins L, Stout L, Prinsen MJ, Griggs DW, Rauchman M. Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury. Physiol Rep. 2020;8(7):e14329.
[4] Fausther M, Dranoff JA. Integrins, myofibroblasts, and organ fibrosis. Hepatology. 2014;60(2):756-758.
[5] Li M, Zhang J, Xiao S, et al. Odontogenesis-associated phosphoprotein (ODAPH) Promotes Ameloblast adhesion and alkaline phosphatase (ALP) expression via LAMC2/ ITGB6/TGF-β1 signaling pathway. PLoS One. 2025;20(7):e0328263.
[6] Ulmasov B, Noritake H, Carmichael P, Oshima K, Griggs DW, Neuschwander-Tetri BA. An Inhibitor of Arginine-Glycine-Aspartate-Binding Integrins Reverses Fibrosis in a Mouse Model of Nonalcoholic Steatohepatitis. Hepatol Commun. 2018;3(2):246-261.
[7] Scott NR, Thirunavukkarasu S, Rangel-Moreno J, Griggs DW, Khader SA. CWHM-12, an Antagonist of Integrin-Mediated Transforming Growth Factor-Beta Activation Confers Protection During Early Mycobacterium tuberculosis Infection in Mice. J Interferon Cytokine Res. 2022;42(8):421-429.
CWHM-12是一种强效的αV整合素抑制剂，对αvβ8、αvβ3、αvβ6和αvβ1的IC50值分别为0.2、0.8、1.5和1.8nM[1]。αV整合素家族是一类异二聚体跨膜受体，可识别含RGD序列的细胞外基质蛋白，在介导细胞黏附、迁移、TGF-β激活和组织重塑中发挥关键作用[2]。CWHM-12通常用于肝纤维化、肺纤维化及肿瘤微环境等研究[3][4]。
在体外，CWHM-12（1mM；3h）可完全消除小鼠成釉细胞系细胞（ALCs）中牙形成相关磷酸蛋白（ODAPH）介导的Tgfb1上调，并逆转Alpl的表达[5]。
在体内，CWHM-12（100mg/kg/天；4周；微型渗透泵持续皮下输注）可逆转胆碱缺乏、氨基酸限定、高脂肪饮食（CDAHFD）诱导的NASH小鼠模型中已建立的肝纤维化，降低肝脏胶原含量，减少α-SMA阳性的活化肝星状细胞，诱导HSC凋亡，并抑制TGFβ/SMAD3信号传导[6]。CWHM-12（100mg/kg/天；45天；微型渗透泵持续皮下输注）可降低结核分枝杆菌HN878感染的C3HeB/FeJ小鼠的肺和脾脏细菌负荷，减少肺泡巨噬细胞和中性粒细胞同时增加募集型巨噬细胞，抑制iNOS、MIP-2和IL-10的产生，并增强胶原沉积[7]。
| Cell experiment [1]: | |
Cell lines | mouse ameloblast-lineage cells |
Preparation Method | Immortalized mouse ameloblast-lineage cells (ALCs), originally isolated from neonatal C57BL/6J mouse mandibular molars, were cultured in DMEM/F12 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in a 5% CO2 atmosphere. The lentiviral vector system contained CMV promoter and puromycin resistance marker. We used the following constructs: (1) LV18-Odaph-mus (LV-Odaph; insert sequence: 5’-GATGTAGTCACCCCTCCTGG-3’) for Odaph overexpression; (2) LV18-NC (LV-NC) as negative control; and (3) LV3-NC (shNC) as scramble control. ALC cells were transduced with respective lentiviruses in medium containing 5μg/mL polybrene to enhance transduction efficiency. ODAPH expression level was quantified by Quantitative real-time PCR (qRT-PCR) and western blot at 72 hours post-transduction. Then cells were treated with either: (1) 1mM CWHM-12 or (2) vehicle control (0.1% DMSO) for 3h to assess acute inhibition effects by qRT-PCR. |
Reaction Conditions | 1mM; 3h |
Applications | CWHM-12 completely abolished ODAPH-mediated Tgfb1 upregulation and reversed Alpl expression induction in mouse ameloblast-lineage cells (ALCs). |
| Animal experiment [2]: | |
Animal models | C3HeB/FeJ (FeJ) mice |
Preparation Method | 6-8 weeks C3HeB/FeJ (FeJ) mice were used in this experiment. Mtb strain HN878 was cultured in Proskauer Beck medium containing 0.05% Tween 80 to mid-log phase and frozen in 2mL aliquots at -80℃. Mice were aerosol infected with 100Mtb colony-forming units (CFUs). At 30 days postinfection (dpi), organs were harvested, homogenized, and serial dilutions of tissue homogenates were plated on 7H11 agar plates, and CFU was determined. CWHM-12 was solubilized in 50% dimethyl sulfoxide (DMSO; in sterile water) and dosed to 100mg/kg body weight per day. Drug or vehicle (50% DMSO) was delivered by implantable ALZET osmotic minipumps. Pumps were inserted subcutaneously; CWHM-12 was delivered by continuous infusion at 100mg/kg/day, and lungs were harvested at 14, 30, and 45 dpi. Lungs from Mtb-infected mice were perfused with 10% neutral buffered formalin and were paraffin embedded for histological analysis. IL-10 and MIP-2 protein levels in lung homogenates were measured using a mouse Luminex assay. |
Dosage form | 100mg/kg/day; 45 days; continuous subcutaneous infusion via ALZET osmotic minipumps |
Applications | CWHM-12 reduced lung and spleen bacterial burden, suppressed MIP-2 and IL-10 production, and enhanced collagen deposition in Mycobacterium tuberculosis HN878-infected C3HeB/FeJ mice. |
References: | |
| Cas No. | 1564286-55-0 | SDF | |
| 化学名 | (2S)-3-[(2-aminoacetyl)-[3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]benzoyl]amino]-2-(3-bromo-5-tert-butylphenyl)propanoic acid | ||
| Canonical SMILES | CC(C)(C)C1=CC(=CC(=C1)C(CN(C(=O)CN)C(=O)C2=CC(=CC(=C2)O)NC3=NCC(CN3)O)C(=O)O)Br | ||
| 分子式 | C26H32BrN5O6 | 分子量 | 590.47 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 1 mg/ml,DMSO:PBS(pH 7.2) (1:2): 0.33 mg/ml | 储存条件 | Store at -20°C |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6936 mL | 8.4678 mL | 16.9357 mL |
| 5 mM | 338.7 μL | 1.6936 mL | 3.3871 mL |
| 10 mM | 169.4 μL | 846.8 μL | 1.6936 mL |
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2.
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