collagen 1

Sinefungin (Adenosyl-Ornithine) is an effective inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication. Sinefungin is a SET7 9 inhibitor and ameliorates renal fibrosis by inhibiting H3K4 methylation.

Collagen proline hydroxylase inhibitor-1 exhibits antifibroproliferative activity.

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

This is a peptide inhibitor of collagen fibrillar matrix assembly.

Halofuginone (RU-19110), the competitive inhibitor of prolyl-tRNA synthetase(Ki=18.3 nM), could also down-regulate Smad3 and blocked TGF-β signaling at 10 ng/ml in the mammal.

SRI-011381 hydrochloride, a new-type agonist of the TGF-beta signaling pathway, is utilized in the treatment of Alzheimer's disease.

Tipelukast (KCA 757) is a novel, orally available leukotriene receptor antagonist with anti-inflammatory properties, capable of reducing fibrosis and down-regulating TIMP-1 and type 1 collagen. Tipelukast is utilized in asthma research.

3-Aminopropionitrile fumarate (2:1) [β-Aminopropionitrile fumarate] is an organic compound and antirheumatic agent utilized in veterinary medicine.

4-Deoxypyridoxine (4-DPD) is a vitamin B6 antimetabolite with diverse biological activities. It inhibits transport of pyridoxine , pyridoxal, and pyridoxamine in and reduces growth of S. carlsbergensis cells. 4-DPD inhibits sphingosine-1-phosphate (S1P) lyase and reduces cyclic stretch-induced apoptosis in alveolar epithelial MLE-12 cells. 4-DPD (5 mg, i.p.) reduces lysyl oxidase activity by 26% and reduces collagen and elastin crosslinking, resulting in limb abnormalities in chick embryos. It decreases latency to first seizure in mice (ED50 = 1 mmol kg) and increases the occurrence and duration of myoclonic responses in baboons with photosensitive epilepsy. 4-DPD reduces TNF-α and IL-6 production in mice infected with T. spiralis.

JTE-952 is a oral, potent active and selective Type II inhibitor of colony stimulating factor-1 receptor (CSF-1R or cFMS, type III receptor tyrosine kinase), with IC50 values of 13 nM and 261 nM for CSF1R and TrkA , respectively. Effective against a mouse

ALK5-IN-82 is a potent and selective inhibitor of activin receptor-like kinase 5 (ALK5), demonstrating an IC50 value of 9.1 nM. This compound effectively suppresses the expression of α-smooth muscle actin (α-SMA), collagen I, and the proteinases tissue inhibitor of metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 13 (MMP-13) in human umbilical vein endothelial cells induced by transforming growth factor-β. ALK5-IN-82 shows potential for use in research related to cardiac fibrosis.

Fibrostat (Compound 5n) is a selective HDAC6 inhibitor that exerts antifibrotic effects by hindering HDAC6 activity, with an IC50 value of 63 nM for HDAC6. It exhibits superior selectivity over HDAC1, HDAC3, HDAC5, HDAC8, HDAC10, and HDAC11. Fibrostat effectively reduces the expression of fibrosis markers, fibronectin and collagen 1, in fibroblasts. It shows no toxicity in rat perfused heart and zebrafish larvae studies. Fibrostat holds promise for research on fibrosis-related diseases.

ERBB agonist-1 (Compound EF-1) is an ERBB4 agonist that activates the ERBB4 signaling pathway by inducing ERBB4 receptor dimerization, with an EC50 of 10.5 μM. It promotes phosphorylation of Akt and ERK1 2, reduces collagen expression in cardiac fibroblasts, and inhibits H2O2-induced cardiomyocyte death and Ang II-induced cardiac hypertrophy. Furthermore, ERBB agonist-1 can prevent myocardial fibrosis and demonstrates cardioprotective effects in mouse models.

FGFRs-IN-1 (Compound A16) is an orally active inhibitor targeting FGFR1 2 3 4, with IC50 values of 2.3, 7, 11, and 163 nM respectively. It also inhibits VEGFR1 2 3, Abl, and Flt3, with IC50 values of 61, 176, 112, 26, and 353 nM. The compound shows weak inhibition of CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and it inhibits epithelial-mesenchymal transition (EMT) in A549 cells stimulated by TGF-β1. Additionally, FGFRs-IN-1 demonstrates anti-inflammatory activity in mouse models of lung fibrosis induced by Bleomycin and liver fibrosis induced by CCl4.

ATX-IN-1 (compound 35) is an ATX inhibitor with an IC50 of 0.7 nM, demonstrating anti-inflammatory properties. It effectively suppresses the TGF-β Smad pathway and reduces collagen deposition, alleviating fibrosis in a Bleomycin-induced mouse model. This compound also exhibits good oral bioavailability (F=69.5%) and microsomal stability.

Galectin-3-IN-6 (Compound 12) is an orally active galectin-3 (Gal-3) inhibitor, with an IC50 of 12 nM and a Kd of 13 nM for Gal-3. In a CCl4-induced mouse model of acute liver injury and fibrosis, Galectin-3-IN-6 significantly reduces fibrosis markers collagen-1 and α-smooth muscle actin (αSMA) by 64% and 71%, respectively, demonstrating notable anti-fibrotic activity. Galectin-3-IN-6 is applicable for research in fibrosis-related diseases, cancer, and cardiovascular disorders.

1-Methylnicotinamide is the active metabolite of nicotinamide, formed by nicotinamide N-methyltransferase. 1-Methylnicotinamide induces the secretion of nitric oxide by human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. When administered at a dose of 30 mg/kg, it can increase the level of 6-keto-prostaglandin F1α in rat plasma and inhibit collagen-induced thrombosis at the same dose.

SP-100030 is a dual inhibitor of NF-κB and activator protein-1 (AP-1), demonstrating potent inhibition with IC50 values of 50 nM for both. It effectively reduces the production of IL-2, IL-8, and TNF-alpha in Jurkat and other T cell lines. Additionally, SP-100030 has been shown to decrease the severity of murine collagen-induced arthritis (CIA).

Allylpyrocatechol is an antioxidant. Allylpyrocatechol attenuates collagen-induced arthritis via attenuation of oxidative stress secondary to modulation of the MAPK, JAK/STAT, and Nrf2/HO-1 pathways.

Diethyl pyimDC is an inhibitor of human collagen prolyl 4-hydroxylase 1 (CP4H1).

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)

SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity.References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019). SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity. References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019).

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

4-hydroxy Valsartan is a major metabolite of the angiotensin II type 1 (AT1) receptor antagonist valsartan . It reduces platelet aggregation induced by epinephrine and collagen but not ADP in human whole blood.