integrin-in-2

Integrin-IN-2 is an orally bioavailable pan αv integrin inhibitor.Integrin-IN-2 can increases the αvβ6, αvβ3, αvβ5 and αvβ8 binding affinities with pIC50 values of 7.8, 8.4, 8.4 and 7.4, respectively.

αvβ1integrin-IN-2（compound 32）作为整合素ανβ1与α5β1的抑制剂，展现出高效性，其IC50值分别为0.9 nM和33 nM。此外，该化合物对其他整合素亦有抑制作用，其IC50分别为380 nM（ανβ3）、280 nM（ανβ5）、230 nM（ανβ6）、87 nM（ανβ8）。

αvβ5integrin-IN-2 (Cpd_AV2) 作为一种αvβ5整合素抑制剂，主要通过破坏整合素异二聚体的稳定性发挥作用。该化合物特异性靶向 ITGAV（整合素 αV）β 螺旋桨的中央口袋，从而能有效诱导细胞凋亡 (apoptosis)。

Glaucocalyxin A (Leukamenin F) 是来自日本黑纹病菌的一种对映型月桂基二萜，具有抗肿瘤作用。它通过调节PI3K Akt 信号通路抑制 GLI1 的核易位，诱导骨肉瘤凋亡。

Chelidonine (Stylophorin) 是白屈菜中的一种异喹啉生物碱，有抗肿瘤和抗病毒作用。它可导致细胞周期 G2 M 停滞，诱导 caspase 依赖和非依赖性的细胞凋亡。

αvβ1 integrin-IN-1 TFA 是一种有效的αvβ1整合素抑制剂(IC50: 0.63 nM)。

2-Methylbutyrylcarnitine (chloride) 作为一种支链酰基肉碱，是肠道微生物代谢的产物。它通过结合血小板中的整合素α2β1，不仅促进细胞质磷脂酶 A2 (cPLA2) 的活化，而且增强了血小板的过度反应性。此外，实验表明，2-Methylbutyrylcarnitine (chloride) 能显著提升小鼠血小板的超反应性和血栓形成能力。

αvβ6-IN-2 (compound 20) 作为一种αvβ6整合素抑制剂，显示出高效和口服活性，其pIC50值达到7.8。此化合物在特发性肺纤维化研究中展示了应用潜力。

Integrin modulator 1 is a potent and selective α4β1 integrin agonist, with an IC50 of 9.8 nM for RGD-binding α4β1. Integrin modulator 1 increases cell adhesion mediated by α4β1 integrin, with an EC50 of 12.9 nM[1]. Integrin modulator 1 (2-10 μg mL; 30 min) significantly increases Jurkat E6.1 cell adhesion[1].Integrin modulator 1 (1-100 nM; 1 h) strongly and significantly increases ERK1 2 phosphorylation in Jurkat E6.1 cells[1].Integrin modulator 1 (1 nM-10 μM; 30 min) significantly increases the binding of HUTS-21 antibody to Jurkat E6.1 cells in a concentration-dependent manner[1]. [1]. Baiula M, et, al. New β-Lactam Derivatives Modulate Cell Adhesion and Signaling Mediated by RGD-Binding and Leukocyte Integrins. J Med Chem. 2016 Nov 10;59(21):9721-9742.

Echistatin TFA, the smallest active RGD protein belonging to the family of disintegrins that are derived from snake venoms, is a potent inhibitor of platelet aggregation. Echistatin is a potent inhibitor of bone resorption in culture. Echistatin is a potent antagonist of αIIbβ3, αvβ3 and α5β1[1][2][3][4]. [1]. J Musial, et al. Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins. RGD-containing peptides from viper venoms. Circulation. 1990 Jul;82(1):261-73.[2]. M Sato, et al. Echistatin is a potent inhibitor of bone resorption in culture. J Cell Biol. 1990 Oct;111(4):1713-23.[3]. C C Kumar, et al. Biochemical characterization of the binding of echistatin to integrin alphavbeta3 receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):843-53.[4]. I Wierzbicka-Patynowski, et al. Structural requirements of echistatin for the recognition of alpha(v)beta(3) and alpha(5)beta(1) integrins. J Biol Chem. 1999 Dec 31;274(53):37809-14.

BIO5192 hydrate is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd<10 pM). BIO5192 hydrate selectively binds to α4β1 (IC50=1.8 nM) over a range of other integrins. BIO5192 hydrate results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels[1][2]. The combination of BIO5192 hydrate (1 mg kg; i.v.) and Plerixafor (5 mg kg; s.c.) exert an additive effect on progenitor mobilization[1].BIO5192 hydrate (30 mg kg; s.c; bid; during days 5 through 14) delays paralysis associated with EAE (experimental autoimmune encephalomyelitis)[2].BIO5192 hydrate (1 mg kg, i.v.) shows the terminal half-life is 1.1 hours. BIO5192 hydrate (3, 10, and 30 mg kg; s.c.) shows half-lives of 1.7, 2.7, and 4.7 hours, respectively. The blood plasma curves show that the AUC for the s.c. route of administration increased about 2.5-fold from 5,460 h*ng ml for the 3 mg kg dose to 14,175 h*ng ml for the 30 mg kg[1]. Animal Model: C57BL 6J x 129Sv J F1 mice[1] [1]. Ramirez P, et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009;114(7):1340‐1343. [2]. Leone DR, et al. An assessment of the mechanistic differences between two integrin alpha 4 beta 1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther. 2003;305(3):1150-1162.

Nexinhib20 是一种外泌体合成和运输的抑制剂，具有抗炎活性，抑制 RAB27A 和中性鞘磷脂酶 2 （nSMase2） nsMase2，抑制 IL-8 诱导的 β（2） 整合素依赖性人中性粒细胞在流下粘附，通过拮抗 rac-1-鸟苷 5'-三磷酸相互作用来抑制中性粒细胞粘附和 β（2） 整合素激活。

ILK-IN-2 (OSU-T315) 是一种新型强效口服活性的整合素连接激酶（ILK）抑制剂，IC50 为 0.6 μM。

Cilengitide TFA 是一种选择性的 αvβ3和 αvβ5受体整合素抑制剂，IC50分别为 4 nM 和 79 nM。对 GP IIb IIIa 的选择性约为 10 倍。

GRGDSPK TFA (EMD 56574 TFA) 是一种含有精氨酸-甘氨酸-天冬氨酸 (RGD) 序列的多肽。作为竞争性且可逆的抑制剂，它能够抑制整联蛋白与纤连蛋白的结合，用于探究整联蛋白在骨形成及吸收过程中的功能。

RGD peptide (GRGDNP) TFA 作为整合素-配体之间相互作用的竞争性抑制剂，阻碍α5β1与细胞外基质(ECM)的结合，并通过激活增强pro-caspase-3的自我加工和构象变化来促进细胞凋亡。该化合物在细胞粘附、迁移、生长和分化等过程中扮演着关键角色。

RGD-4C（ACDCRGDCFC）是一种携带Arg-Gly-Asp（RGD）序列的肽，具备与αv整合素结合的能力，用于模拟细胞外基质蛋白的整合素识别特性。作为αv整合素的配体，它能够与生物活性分子进行偶联，进而在动物模型中展现出抗肿瘤活性。

QLT0267 is an inhibitor targeting integrin-linked kinase (ILK; IC50= 26 nM), showing over 10-fold selectivity against cyclin-dependent kinases 1, 2, and 5 (Cdk1, Cdk2, and Cdk5), and over 1,000-fold selectivity against C-terminal Src kinase (CSK), DNA-PK, Pim-1, Akt, PKC, and casein kinase 2 (CK2) at a concentration of 10 mg/ml. This compound effectively inhibits the proliferation of NPA187 papillary thyroid cancer cells with an IC50 of approximately 3 µM and induces apoptosis in NPA187, DRO, and K4 cancer cell lines. In vivo studies reveal that QLT0267, administered at 100 mg/kg, significantly reduces tumor growth in a DRO mouse xenograft model and diminishes both tumor volume and intratumoral vascularization in a U87MG glioblastoma mouse xenograft model, showcasing its potential for therapeutic applications in cancer treatment.

KIN-8194是一种具有口服活性的HCK和BTK双重抑制剂，IC50值分别为0.915和0.495 nM。KIN-8194损害BTKi耐药性套细胞淋巴瘤 (MCL) 的生长和整合素介导的粘附，克服ibrutinib耐药性，并在TMD-8 ABC DLBCL异种移植小鼠中具有生存获益。

α4integrinreceptor antagonist 3(Compound 11)是一种口服活性的α4整合素受体拮抗剂.该化合物能有效抑制 K562 细胞通过α4β1 VCAM-1和α4β7 MAdCAM-1相互作用的粘附,其IC50值分别为 130 nM 和 2 nM.此外,α4integrinreceptor antagonist 3 在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型中显示了研究潜力.

Ac-MRGDH-NH2 是一种含有 RGD 的五肽，用于合成非对映异构体前药 Λ- 和 Δ-[Ru(Ph2phen)2(κS,κN-(Ac-MRGDH-NH2))]Cl2。在这些前药中，Ac-MRGDH-NH2 可作为细胞毒性双水合钌弹头 [Ru(Ph2phen)2(OH2)2]2+ 的光裂解保护基，并具备整合素靶向性和光取代性。因此，可用于肿瘤靶向光活化化疗研究。