Angiogenesi

Donafenib(Bay 43-9006 (D3)) is a deuterium-labeled Sorafenib which is a multikinase inhibitor(IC50s: 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3,

Tivozanib hydrochloride hydrate (AV-951 hydrochloride hydrate) is a VEGFR tyrosine kinase inhibitor that inhibits VEGFR-1, VEGFR-2, VEGFR-3 .

<p>Stability Hygroscopic<br>Applications Dihydrochloride salt of trans-3-Hydroxy Apatinib, a metabolite of the antiangiogenic agent and selective VEGFR2 inhibitor Apatinib (A726150).<br>References Ding, J, et al.: J. Chrom B Anal. Technol. Biomed. Life Sci., 895, 108 (2012);<br></p>

<p>Seribantumab (MM 121) is a humanized monoclonal antibody targeting HER3, inhibiting cancer cell proliferation.</p>

Obtustatin triacetate is an integrin derived from the venom of Vipera lebetina obtusa and is an α1β1 integrin and in vivo angiogenesis inhibitor.

Dapolsertib (SEL24-B489) is an orally active and efficient PIM and FLT3-ITD inhibitor, reducing PIM-specific substrate phosphorylation.

<p>Applications Glycerol 1-Monobutyrate functions as a key regulatory molecule in angiogenic process.<br>References Dobson, D. E., et al.: Cell (Cambridge, MA, U. S.), 61, 223 (1990)<br></p>

<p>Applications N-Acryloyl Osimertinib is used in the preparation of pyrimidinyl indole derivative as EGFR inhibitor for targeted therapy of cancer<br>References Rao, Y., et al.: Faming Zhuanli Shenqing (2016), CN 105777716 A 20160720<br></p>

Osunprotafib (ABBV-CLS-484) is a potent, orally bioavailable PTP1B/PTPN2 inhibitor in clinical trials for solid tumors.Cost-effective and quality-assured.

Itacnosertib (TP-0184) is an orally available ACRV1 (ALK-2), FLT3 and JAK2 inhibitor that inhibits the growth of tumor cells,antitumor and antileukemic.

AZ 12799734 is an orally active, selective and potent dual inhibitor of TGFBR1 and ALK5 with inhibitory effects on BMP and TGFβ for the study of tumours.

<p>Cavutilide has antiarrhythmic activity, inhibits hERG K(+) channels, and can be used to study heart failure and persistent atrial fibrillation.</p>

<p>Applications α-Eudesmol is an isomer of β-Eudesmol (E938600), a sesquiterpenoid known to induce neurite outgrowth. β-Eudesmol exhibits antiangiogenic activity.<br>References Obara, Y. et al.: J. Pharmacol. Exp . Ther., 30, 803 (2011); Tsuneki, H. et al.: Eur. J. Pharmacol., 512, 105 (2005);<br></p>

SB-505124 hydrochloride (SB505124 hydrochloride) is a TGF-β type I receptor (ALK4, ALK5, ALK7) inhibitor for the study of colorectal cancer.

Syk inhibitor II, a cell-permeable, ATP-competitive, pyrimidine-carboxamide compound, selectively and reversibly inhibits Syk (IC50 = 41 nM).

Gefitinib-d6 is a deuterated compound of Gefitinib. Gefitinib has a CAS number of 184475-35-2. Gefitinib is an EGFR tyrosine kinase inhibitor and can inhibit Tyr1173, Tyr992, Tyr1173 and Tyr992 (IC50s: 37/37/26/57 nM).

BMS-690514 is a potent and orally active inhibitor of EGFR and VEGFR. It has IC50s of 5, 20 and 60 nM for EGFR, HER 2 and HER 4, respectively.

Naquotinib mesylate (ASP8273 (mesylate)) is an orally available, mutant-selective and irreversible inhibitor of EGFR(iC50s of 8-33 nM and 230 nM for toward EGFR

BIBF 1202 is a VEGFR2 kinase inhibitor (IC50 = 62 nM).

Canertinib dihydrochloride (PD-183805 dihydrochloride) is the hydrochloride salt of an orally bio-available quinazoline with potential antineoplastic and

Brivanib Alaninate (BMS-582664) is an alaninate salt of a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with potential antineoplastic effect.

<p>Applications 5-[(4-Hydroxyphenyl)methylene]-2,4-thiazolidinedione is a 5-Benzylidene-2,4-thiazolidenedione derivative designed as inhibitors of angiogenesis targeting VEGFR-2. Also, it is an intermediate used in the synthesis of MSDC 0602 (M755420), which is an analogue of thiazolidinediones, exhibits low affinity for binding and activation of peroxisome proliferator-activated receptor γ (PPARγ). Thiazolidinediones are effective insulin-sensitizing drugs for treating various metabolic and inflammatory diseases.<br>References Bhanushali, U., et al.: Bioorg. Chem., 67, 139-147 (2016); Chen, Z., et al.: J. Biol. Chem. 287, 23537 (2012); Fukunaga, T., et al.: J. Bone Miner. Res., 30, 508 (2015)<br></p>

<p>Imgatuzumab (RG 7160) is a humanized anti-EGFR monoclonal antibody and immunomodulator for cancer research.</p>

Runimotamab, an IgG1-κ humanized chimeric antibody, targets CD3E and HER2 [1].

Anti-Mouse VEGFR-2 Antibody (DC101) is a rat-derived monoclonal antibody against mouse VEGFR2/KDR/Flk-1, serving as a mouse analogue of ramucirumab.

<p>Depatuxizumab is a humanised monoclonal antibody targeting EGFR with blood-brain barrier (BBB) permeability, inhibit tumor growth,GBM,SCCHN.</p>

<p>Becotatug (JMT-101) is an IgG1 antibody that targets EGFR and can be conjugated to Afatinib and Osimertinib, functioning as a synthetic antibody-drug conjugate</p>

<p>Vanucizumab is a bispecific humanised monoclonal antibody that simultaneously inhibits the receptor interactions of VEGF-A and Angiopoietin-2 (Ang-2)</p>

<p>Serclutamab, a humanized chimeric monoclonal antibody of the IgG1-κ isotype, selectively targets the epidermal growth factor receptor (EGFR).</p>

Fidasimtamab, a recombinant human IgG1 bispecific antibody, targets both HER2 and PD-1, bridging T cells and tumor cells to modulate immune responses.

Elgemtumab (LJM716) is a fully humanised monoclonal antibody targeting HER3/ERBB3, acting as an antagonist to block HER3/Akt phosphorylation antitumour.

Solrikitug,Anti-CRLF2 humanized IgG1κ monoclonal antibody.

Tovetumab (MEDI-575) is an anti-PDGFRα mAb inhibiting its signaling, in trials for glioblastoma and NSCLC.

Bafisontamab (EMB-01) is a bispecific antibody that targets EGFR and cMET, displaying antitumor activity [1].

Zalutumumab is a high-affinity fully human monoclonal antibody ,the extracellular domain of the EGFR squamous cell carcinoma of the head and neck (SCCHN).

Ivonescimab (AK112) is a PD-1/VEGF bispecific antibody with cancer immunotherapy and anti-angiogenic effects, NSCLC).

Dilpacimab (ABT165) is a dual-variable antibody that targets DLL4 and VEGF pathways, showing potential in cancer research by blocking angiogenesis and Notch.

Zanidatamab (ZW25) is a bispecific, humanized monoclonal antibody that targets two distinct epitopes (ECD2 and ECD4) of the HER2 receptor, exhibiting anti-tumor

Fepixnebart is a humanized IgG4κ antibody that targets TGF-alpha (TGFA).

Izalontamab (SI-B001) is a bispecific EGFR/HER3 monoclonal antibody that binds to both EGFR×EGFR homodimers and EGFR×HER3 heterodimers.

Ponezumab (PF-04360365), a humanized IgG2 antibody, lowers Aβ in the CNS & boosts mice memory. Used in Alzheimer's research.

Anbenitamab (KN-026) is a bispecific HER2 antibody for metastatic breast cancer research, blocking HER2 pathways and mediating ADCC.

EGFRT790M/L858R-IN-8 (compound 9) is a potent inhibitor of EGFR, specifically targeting the EGFRT790M/L858R mutations with an IC50 of 56.8 μM. This compound does not show significant antiproliferative effects on cancer cell lines A549, A431, and NHI-H1975.

Tarcocimab (OG1953) is a humanized IgG1 monoclonal antibody targeting VEGFA, researched for RVO and wet AMD.

Futuximab is a chimeric monoclonal antibody targeting EGFR, commonly used in combination with zatuximab to form Sym004.

Faricimab,Bispecific antibody targeting Ang-2/VEGF-A. Prevents retinal I/R injury. Improves vision in w-AMD, DME, RVO.

Ibrutinib D5 is a deuterium-labeled Ibrutinib. Ibrutinib is an irreversible Btk inhibitor.

Dasatinib D8 is deuterium-labeled dasatinib. Dasatinib is a dual Bcr-Abl and Src family tyrosine kinase inhibitor.

Apatinib-d8 is a deuterated compound of Apatinib. Apatinib has a CAS number of 811803-05-1. Apatinib is an orally bioavailable and specific VEGFR2 inhibitor (IC50: 1 nM). In addition, this agent mildly inhibits c-Kit and c-SRC tyrosine kinases.

MAPK-IN-2 (compound 3h) is an efficacious MAPK inhibitor with antineoplastic properties that significantly hinders proliferation across various cancer cell

ZM323881 hydrochloride (ZM 323881 HCl) is a potent and selective VEGFR2 inhibitor.

EGFR-IN-109 (compound 4), an EGFR inhibitor, displays IC 50 values of 25.8 nM for EGFR WT and 182.3 nM for EGFR T790M. This compound halts the growth of cancer cells at the G2/M phase and triggers both early and late apoptosis. It is applicable in cancer research [1].

Icotinib (Conmana) is an orally available quinazoline-based inhibitor of epidermal growth factor receptor (EGFR), with potential antineoplastic activity.

Dovitinib dilactic acid: multitarget RTK inhibitor for FLT3/c-Kit (IC50=1-2 nM), FGFR1/3, VEGFR1-4 (IC50=8-13 nM), less effective on InsR, EGFR. Phase 4.

GZD856 formic inhibits PDGFRα/β (IC50: 68.6, 136.6 nM) & Bcr-Abl (IC50: 19.9, 15.4 nM), with antitumor properties.

HVH-2930 is an inhibitor of Heat Shock Protein 90 (HSP90). It suppresses the cell viability of BT474 (Trastuzumab sensitive) and JIMT-1 (Trastuzumab resistant) by downregulating HSP90 client proteins such as HER2, p-HER2, AKT, p-AKT, cyclin D1, and survivin, with IC50 values of 6.86 μM and 4.42 μM, respectively. Additionally, HVH-2930 demonstrates antitumor efficacy in a mouse model and exhibits favorable pharmacokinetic properties in vivo.

ALK5-IN-79 (compound 57), an ALK inhibitor, exhibits anticancer activity by inhibiting the TGF-β1/SMAD signaling pathway. It effectively reduces the production of extracellular matrix (ECM) and collagen deposition. Moreover, ALK5-IN-79 demonstrates satisfactory pharmacokinetic (PK) properties and favorable in vivo tolerance.

(3S,4S)-Tofacitinib, a less active enantiomer of tofacitinib, is a Janus kinases inhibitor.

<p>Erlotinib: reversible inhibitor binding to ATP site of epidermal growth factor receptor.</p>

<p>IGF-1Rmodulator 1 (Example 5) is an IGF-1R modulator featuring an EC50 of 0.29 μM (FGFR1), 0.25 μM (IGF1R), 0.34 μM (TrkA), and 0.39 μM (TrkB). This compound is useful in research on diseases characterized by impaired signaling of neurotrophic and/or other trophic factors, such as Alzheimer's disease.</p>

EGFR-IN-117 (Compound 8h) exhibits inhibitory activity against EGFR mutations, specifically targeting the tumor environment and inducing apoptosis in cancer cells. This compound effectively inhibits the proliferation of H1975, PC-9, and mutant EGFR cells including BaF3-EGFRL858R/T790M/C797S and BaF3–C797S/Del19/T790M, with IC50 values of 13 nM, 19 nM, 1.2 nM, and 1.3 nM respectively. Additionally, EGFR-IN-117 demonstrates anti-tumor activity in mouse models.

<p>AD1058 is a selective ATR inhibitor that crosses the blood-brain barrier with in vivo anticancer activity, used in the study of brain and CNS metastasis.</p>

ZM39923 is a JAK3 inhibitor (pIC50: 7.1). ZM39923 also effectively inhibits tissue transglutaminase (IC50: 10 nM).

<p>Applications 2-Chloro-N-[4-(1-cyanocyclopentyl)phenyl]-3-pyridinecarboxamide is an intermediate Apatinib 25-N-Oxide (A726160), a metabolite of the antiangiogenic agent and selective VEGFR2 inhibitor Apatinib (A726150).<br></p>

<p>Applications Pulsatilla Saponin D shows antiangiogenic and antitumor activity.<br>References Sang-Won, H. et al.: Carcinogen., 34, 2156 (2013);<br></p>

<p>Applications Tyrphostin AG 112 is an EGFR inhibitor.<br></p>

<p>Applications 6-Amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile, is used in the synthetic preparation of aminopropanamides which is used in irreversible inhibition of epidermal growth factor receptor (EGFR) for potential use in cancer therapy.<br>References Carmi, C., et al.: J. Med. Chem., 55, 2251 (2012)<br></p>

<p>Stability Moisture Sensitive<br>Applications 2,3-Naphthalic anhydride is used as a reagent to synthesize analogues of Thalidomide (T338850), an inhibitor of tumour necrosis factor that was once abandoned because it caused birth defects, but is currently used as an inhibitor of angiogenesis in patients with multiple myeloma.<br>References D’Amato, R., et al.: Proc. Nat. Acad. Sci., 91, 4082 (1994); Ehrenpreis, E., et al.: Gastroenterology, 117, 1271 (1999); Parma, T., et al.: Nat. Med., 5, 582 (1999); Singhal, S., et al.: New Engl. J. Med., 341, 1565 (1999)<br></p>

<p>Applications LB 42708 is a selective nonpeptidic Farnesyltransferase (FTase) inhibitor.LB42708 suppresses tumor growth and tumor angiogenesis in both xenograft tumor models of Ras-mutated HCT116 cells and its wild-type Caco-2 cells, indicating its potential application in the treatment of both Ras-mutated and wild type tumors.<br>References Kim, C., et. al.: Mol. Pharmacol., 78, 142 (2010)<br></p>

<p>Applications 4-Fmoc-3(R)-morpholinecarboxylic Acid is used to prepare 125I-labeled morpholine-containing RGD ligand of αvβ3 integrin as angiogenesis imaging probe.<br>References Bianchini, F., et al.: J. Med. Chem., 55, 5024 (2012)<br></p>

<p>Applications Atrasentan is a selective antagonist of the endothelin-A (ETA) receptor and binds selectively to the ETA receptor, which may result in inhibition of endothelin-induced angiogenesis and tumor cell proliferation.<br>References Bax, W., et al.: Trends Pharmacol. Sci., 15, 379 (1994); Winn, M., et al.: J. Med. Chem., 39, 1039 (1996); Wu-Wong, J., et al.: J. Pharmacol. Exp. Ther., 281, 791 (1997);<br></p>

<p>Applications Tyrphostin AG 1478 is a potent and selective inhibitor of EGFR.<br></p>

CP-547632 is an oral ATP-competitive inhibitor of VEGFR-2/FGF kinase with IC50s of 11/9 nM, highly selective, has antitumor activity.

Icotinib Hydrochloride, an oral EGFR inhibitor (BPI-2009H), may halt cancer growth by blocking EGFR signaling.

SU11274 (Met Kinase Inhibitor)(IC50=10 nM) is a specific Met inhibitor. It shows no significant effects on PGDFRβ, EGFR or Tie2.

Bucillamine (DE019) protects against Ischemia/reperfusion injury in high-risk organ transplants and inhibits the production of VEGF.

E3330 is a potent and selective APE1(Ref-1) inhibitor, which suppressed NF-kappa B DNA-binding activity.

GW843682X (GW843682) is a selective and ATP-competitive inhibitor of PLK1 and PLK3 (IC50s = 2.2 nM and 9.1 nM).

TAK-285 is a novel dual HER2 and EGFR(HER1) inhibitor, >10-fold selectivity for HER1/2 than HER4, less potent to MEK1/5, c-Met, Aurora B, Lck, CSK etc.

DMH4 is a potent and selective inhibitor of VEGFR2 with an IC50 of 0.16 µM.

TGFBR1-IN-1 is an inhibitor of ALK5 (IC50 of 10-100 nM).

Antiproliferative agent-30 (Compound 8g) demonstrates broad-spectrum antiproliferative activity, with IC50 values of 0.054 nM, 0.008 nM, and 0.144 nM against

BTK-IN-24 is a Bruton's tyrosine kinase (BTK) inhibitor with potential anticancer activity, and it can be used in the study of myeloproliferative disorders.

THS-044 (N-[2-Nitro-4-(Trifluoromethyl)phenyl]morpholin-4-Amine) binding stabilizes the HIF2α PAS-B folded state with a kd of 2 μM and regulates HIF2 activity

PDGFRβ inhibitor

EGFR-IN-68, an EGFR inhibitor, has an IC50 of 0.33 μM and shows significant anticancer effects.

<p>FM19G11 is an inhibitor of hypoxia inducible factor (HIF) α-subunit (IC50 = 80 nM in hypoxia induced luciferase assay).</p>

BKI-1369 is a bumped kinase inhibitor. BKI-1369 increases hERG-inhibitory activity (IC50:1.52 μM).

ACP-5862, active metabolite of Acalabrutinib, is a BTK inhibitor with an IC50 of 5.0 nM.

<p>NSC114126 is a potent, oral EGFR-TK inhibitor with strong antiproliferative effects, promising for cancer research.</p>

EGFR-IN-50, a potent EGFR blocker, hinders L858R mutation; GI50: 8 nM for TEL-EGFR-L858R, 6.03 μM for T790M-L858R; curbs cancer cell growth.

FLT3-IN-15 is an orally active and potent FLT3 inhibitor, capable of acting on FLT3 (IC50: 0.87 nM) and FLT3/D835Y (IC50: 0.32 nM).

ALK5-IN-30 (EX-07) is a potent inhibitor of ALK with inhibitory effects on ALK5 (IC50< 10 nM) and TGFβ-R1 (IC50< 10 nM).

NSC81111 shows anticaner effects which is a potent and orally active inhibitor of EGFR-TK (IC50 = 0.15 nM) [1].

Naphazoline (Naphcon-a) is a sympathomimetic compound with marked alpha adrenergic activity.

CJ-2360 is a potent ALK inhibitor, effective on wild-type and various mutants, with IC50 values ranging from 2.2 to 8.9 nM, also targeting 468 kinases.

SJF620 is a potent degrader of PROTAC BTK(DC50 : 7.9 nM).