collagen 3

Sinefungin (Adenosyl-Ornithine) 是病毒粒子mRNA (鸟嘌呤-7-)-甲基转移酶、 mRNA (核苷-2'-)-甲基转移酶和病毒增殖的有效抑制剂。它还抑制SET7 9，通过抑制H3K4甲基化来改善肾纤维化。

3-Aminopropionitrile fumarate (2:1) (β-Aminopropionitrile fumarate) 是一种能抑制胶原蛋白(collagen)交联的山黧豆素。

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。

PXS-5153A monohydrochloride 是一种有效的、选择性的、具有口服活性和快速起效的赖氨酰氧化酶 2 3(LOXL2 LOXL3)的双抑制剂，对几乎所有哺乳动物物种 LOXL2的 IC50均< 40 nM，对人类 LOXL3 的 IC50为63 nM。PXS-5153A monohydrochloride 可减少交联并改善纤维化。

GED-0507-34 Levo((S)-3-(4-氨基苯基)-2-甲氧基丙酸)是一种可口服的PPARγ调节剂，用于改善炎症驱动的肠道纤维化，降低了促纤维化基因Acta2、COL1a1和Fn1的表达，减少了纤维化主要标志物α-SMA和胶原蛋白I-II的蛋白水平，以及TGFβ Smad途径的主要成分，降低了IL-13、CTGF、TGFB和ACTA1的表达，抑制了TGF-β诱导的成纤维细胞和IECs细胞系的活化。

TRPV1-IN-3 (compound 14) 是一种用于研究特发性肺纤维化的TRPV1抑制剂。此化合物通过阻断TGF-β Smads和MAPK通路，调节纤维化标志物胶原 I 和α-SMA的表达，从而在体外展现出抗纤维化活性 (IC50=0.51 μM)。TRPV1-IN-3 可有效抑制肺组织中的胶原沉积，改善肺泡结构，并提高Bleomycin诱导的肺纤维化小鼠的存活率。

FGFRs-IN-1 (Compound A16) 是一种有效的口服FGFR抑制剂，可分别抑制FGFR1、FGFR2、FGFR3和FGFR4，其IC50值为2.3、7、11和163 nM。此外，FGFRs-IN-1 同时抑制VEGFR1 2 3、Abl和Flt3，IC50值分别为61、176、112、26和353 nM，然而对CYP酶的抑制作用较弱。该化合物可降低α-SMA和胶原蛋白I (collagen I) 的表达，并在TGF-β1刺激的A549细胞中抑制上皮-间质转化 (EMT)。在Bleomycin诱导的小鼠肺纤维化模型及CCl4诱导的小鼠肝纤维化模型中，FGFRs-IN-1 显示出抗炎活性。

Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg ml) and Gram-negative bacteria (MICs = 136-200 µg ml), as well as yeasts (MICs = 10-20 µg ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16 BL6 mouse model of melanoma when administered at a dose of 25 mg kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg kg.3Ajoene (25 mg kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16 BL6 melanoma cells in C57BL 6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)

Oleic acid-13C is intended for use as an internal standard for the quantification of oleic acid by GC- or LC-MS. Oleic acid is a monounsaturated fatty acid and a major component of membrane phospholipids that has been found in human plasma, cell membranes, and adipose tissue.1,2 It contributes approximately 17% of the total fatty acids esterified to phosphatidylcholine, the major phospholipid class in porcine platelets.1 Oleic acid inhibits collagen-stimulated platelet aggregation by approximately 90% when used at a concentration of 10 μg ml. It also inhibits fMLF-induced neutrophil aggregation and degranulation by 55 and 68%, respectively, when used at a concentration of 5 μM, similar to arachidonic acid .3 Oleic acid (60 μM) induces release of intracellular calcium in human platelets.4

Psychotridine is an alkaloid that has been found inP. forsterianaand has diverse biological activities.1,2,3It inhibits ADP-, collagen-, or thrombin-induced aggregation of washed isolated human platelets with IC50values of 1.4, 1.4, and 3.9 μM, respectively.1Psychotridine (2.5 or 5 μM) is cytotoxic to HTC rat hepatocellular carcinoma cells.2It reduces paw licking induced by capsaicin in mice when administered at doses of 0.5, 2.5, or 5 mg kg.3 1.Beretz, A., Roth-Georger, A., Corre, G., et al.Polyindolinic alkaloids from Psychotria forsteriana. Potent inhibitors of the aggregation of human plateletsPlanta Med.51(4)300-303(1985) 2.Roth, A., Kuballa, B., Bounthanh, C., et al.Cytotoxic activity of polyindoline alkaloids of Psychotria forsteriana (Rubiaceae) (1)Planta Med.6450-453(1986) 3.Amador, T.A., Verotta, L., Nunes, D.S., et al.Involvement of NMDA receptors in the analgesic properties of psychotridinePhytomedicine8(3)202-206(2001)

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 dihydrochloride inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 . RWJ-56110 dihydrochloride blocks angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 dihydrochloride induces cell apoptosis[1][2]. Proteinase-activated receptors (PARs) are a family of G protein-coupled receptors activated by the proteolytic cleavage of their N-terminal extracellular domain, exposing a new amino terminal sequence that functions as a tethered ligand to activate the receptors.RWJ56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM) while being quite selective relative to collagen and the thromboxane mimetic U46619 [1].RWJ-56110 dihydrochloride is fully inhibits thrombin-induced RASMC proliferation with an IC50 value of 3.5 μM. RWJ-56110 dihydrochloride shows blockade of thrombin's action with RASMC calcium mobilization (IC50=0.12 μM), as well as with HMVEC (IC50=0.13 μM) and HASMC calcium mobilization (IC50=0.17 μM)[1].RWJ56110 (0.1-10 μM; 24-96 hours) inhibits endothelial cell growth dose-dependently, with half-maximal inhibitory concentration of RWJ56110 is approximately 10 μM[2].RWJ56110 (0.1-10 μM; 6 hours) inhibits DNA synthesis of endothelial cells in a thymidine incorporation assays. Endothelial cells are in fast-growing state (50-60% confluence), RWJ56110 inhibits cell DNA synthesis in a dose-dependent manner, but when cells that are in the quiescent state (100% confluent), the inhibitory effect of PAR-1 antagonists is much less pronounced[2].RWJ56110 (0.1-10 μM; pretreatment for 15 min) inhibits thrombin-induced Erk1 2 activation in a concentration-dependent manner. However, when endothelial cells are stimulated by FBS (final concentration 4%), it reduces partially the activated levels of Erk1 2[2].RWJ56110 (30 μM; 24 hours) has an inhibitory effect on endothelial cell cycle progression. It reduces the percentage of cells in the S phase, while alterations in the percentages of G1 and G2 M cells are less pronounced[2]. Western Blot Analysis[2] Cell Line: Endothelial cells [1]. Andrade-Gordon, et al.Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. oc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62. [2]. Panagiota Zania, et al. Blockade of angiogenesis by small molecule antagonists to protease-activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006 Jul;318(1):246-54.

Isogarcinol is a natural polyisoprenylated benzophenone first isolated from plant species in the genus Garcinia. It has immunosuppressant actions, inhibiting the protein phosphatase calcineurin (IC50 = 36 μM) and suppressing the proliferation of T cells. Oral administration of isogarcinol in mice decreases delayed type hypersensitivity, prolongs graft survival in allogeneic skin transplants, suppresses inflammation in collagen-induced arthritis, and reduces clinical symptoms in experimental autoimmune encephalomyelitis. Isogarcinol inhibits the proliferation of HL-60 and PC-3 cancer cells (IC50s = 4 and 8 μg ml, respectively) through cell cycle arrest and apoptosis.

Pal-KTTKS is a lipidated pentapeptide consisting of a fragment of the type I collagen C-terminal propeptide conjugated to palmitic acid .1 It increases collagen production in human corneal and dermal fibroblasts when used at concentrations of 0.002, 0.004, and 0.008 wt%.2 Following topical administration, pal-KTTKS (50 μg/cm2) is found in the stratum corneum, epidermis, and dermis of isolated hairless mouse skin.1 It can self-assemble into flat tapes and extended fibrillar structures.3 Pal-KTTKS has been detected in anti-wrinkle creams.4 |1. Choi, Y.L., Park, E.J., Kim, E., et al. Dermal stability and in vitro skin permeation of collagen pentapeptides (KTTKS and palmitoyl-KTTKS). Biomol. Ther. (Seoul) 22(4), 321-327 (2014).|2. Jones, R.R., Castelletto, V., Connon, C.J., et al. Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts. Mol. Pharm. 10(3), 1063-1069 (2013).|3. Castelletto, V., Hamley, I.W., Whitehouse, C., et al. Self-assembly of palmitoyl lipopeptides used in skin care products. Langmuir 29(29), 9149-9155 (2013).|4. Chirita, R.-I., Chaimbbault, P., Archambault, J.-C., et al. Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics. Anal. Chim. Acta 641(1-2), 95-100 (2009).

Collinin is a coumarin that has been found in Z. schinifolium and has diverse biological activities.1,2,3,4 It is active against drug-susceptible and -resistant strains of M. tuberculosis (MIC50s = 3.13-6.25 μg/ml).1 Collinin inhibits LPS-induced nitric oxide (NO) production (IC50 = 5.9 μM) and reduces COX-2 protein levels in RAW 264.7 cells.2 It completely inhibits aggregation of isolated rabbit platelets induced by arachidonic acid , collagen, or platelet activating factor (PAF) when used at a concentration of 100 μM.3 Dietary administration of collinin (0.05% w/w) reduces the number of mice with tumors and the number of tumors per mouse in a mouse model of colitis-related carcinogenesis.4 |1. Kim, S., Seo, H., Al Mahmud, H., et al. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46, 104-110 (2018).|2. Nguyen, P.-H., Zhao, B.T., Kim, O., et al. Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity. J. Nat. Med. 70(2), 276-281 (2016).|3. I.S., C., Lin, Y.C., Tsai, I.L., et al. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39(5), 1091-1097 (1995).|4. Kohno, H., Suzuki, R., Curini, M., et al. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int. J. Cancer 118(12), 2936-2942 (2006).

MMP13-IN-2 is a highly potent, selective, and orally active inhibitor of MMP-13. It demonstrates exceptional potency against MMP-13, with an IC50 value of 0.036 nM, and exhibits selectivities greater than 1,500-fold over MMP-1, 3, 7, 8, 9, 14, and TACE. Moreover, MMP13-IN-2 possesses the capability to effectively inhibit collagen release from cartilage in vitro. Consequently, MMP13-IN-2 holds great potential for advancing research on collagenase-related diseases.

Collagen-IN-1 (compound 3) is an ortho-carbonyl hydroquinone derivative exhibiting selective inhibition of collagen. It non-competitively inhibits agonist-induced platelet aggregation, with an IC50 value of 1.77 μM. Collagen-IN-1 effectively reduces the expression of P-selectin, activation of glycoprotein IIb IIIa, and release of adenosine triphosphate and CD63 from platelets. This compound holds promise for research into platelet-related thrombosis diseases [1].

GPVI antagonist 3 (Compound 2) is a potential antagonist that shows promising antiplatelet activity by selectively inhibiting the interaction between the Glycoprotein VI (GPVI) receptor and its ligands. It demonstrates potent inhibitory effects, with IC50 values of 1.01 μM for collagen, 1.92 μM for CRP, 7.24 μM for convulxin, and 51.74 μM for thrombin. GPVI is a major collagen receptor on platelets, making it an ideal target for safe and effective antithrombotic treatment. Therefore, GPVI antagonist 3 holds potential as a novel antiplatelet agent [1].

Angiotensin II human (Angiotensin II) TFA 作为肾素 血管紧张素系统中关键的生物活性肽，扮演着血管收缩剂的角色并在调节人体血压中发挥中心作用。其主要通过与 G 蛋白偶联受体 (GPCRs)、血管紧张素 II 1型受体 (AT1R) 和血管紧张素 II 2型受体 (AT2R) 的相互作用来介导效应，包括刺激交感神经系统、增加醛固酮的生物合成和肾脏功能。此外，Angiotensin II human TFA 促进血管平滑肌细胞的生长和 I 型及 III 型胶原在成纤维细胞中的合成，导致血管壁与心肌增厚及纤维化，并诱导细胞凋亡。还通过LOX-1依赖的氧化还原敏感路径诱导内皮细胞中的毛细血管形成。

Osteostatin为甲状旁腺激素相关蛋白(PTHrP) 107-111片段，该化合物在动物模型中促进骨缺损修复，预防炎症性关节炎引起的骨侵蚀，并抑制骨胶原诱导的关节炎及破骨细胞的吸收作用。Osteostatin主要应用于免疫炎症的研究领域。

H-Gly-Pro-Hyp-OH是一种有效和可口服的抗光老化胶原肽，能够减轻炎症，降低MMP-1和MMP-3含量；能够减轻H2O2诱导的真皮成纤维细胞老化；能够恢复皮质醇介导的I型胶原蛋白和GR激活的抑制和(TGF)-β信号等抑制；改善人体皮肤的水合性、弹性和抗皱性。

Caprooyl-tetrapeptide-3 acetate 旨在减少细纹与皱纹。该化合物能够在皮质激素诱导的皮肤老化模型中刺激VII型胶原蛋白及层粘连蛋白5的表达。

(±)17(18)-EpETE-Ethanolamide, an ω-3 endocannabinoid epoxide, originates from eicosapentaenoic ethanolamide (EPEA) through cytochrome P450 (CYP) epoxygenases action and is decomposed by soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FA, AH). Its endogenous synthesis occurs in LPS-stimulated and EPEA-supplemented BV-2 microglia cells, a process inhibited by the CYP inhibitor ketoconazole. This compound mitigates IL-6 and nitrite levels while enhancing IL-10 production following LPS exposure in BV-2 microglia. At a dose of 50 µM, it prevents platelet aggregation caused by arachidonic acid but not that triggered by ADP, collagen, or ristocetin. Additionally, it facilitates the dilation of constricted bovine coronary arteries (ED50= 1.1 µM) and blocks VEGF-driven tubulogenesis in human microvascular endothelial cells (HMVECs).

Kartogenin (KGN) sodium 是一种软骨样组织形成的诱导剂 (EC50: 100 nM)。Kartogenin sodium 通过结合纤维蛋白 A，阻断其与转录因子核心结合因子 β 亚基 (CBFβ) 的作用，并调节 CBFβ-RUNX1 转录程序来诱导软骨形成。此外，Kartogenin sodium 能促进肌腱-骨连接处 (TBJ) 的伤口愈合，因其能刺激胶原蛋白合成。广泛应用于再生医学中的无细胞疗法，Kartogenin sodium 用于软骨再生及保护、腱骨愈合、伤口愈合与肢体发育等方面，同时对骨关节炎 (OA) 的研究也颇具价值。

Indirubin-3′-oxime 是一种有效的细胞周期蛋白依赖性蛋白激酶抑制剂，是 indirubin 的合成衍生物。它可通过激活软骨细胞中的 Wnt β-catenin 信号来促进身高增长，可能在阿尔茨海默病的神经元凋亡中发挥作用。