Protein-tyrosine kinases (PTKs) catalyze the transfer of the γ-phosphate of ATP to tyrosine residues of protein substrates, are critical components of signaling pathways that control cellular proliferation and differentiation. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs.

The RTK family includes the receptors for insulin and for many growth factors, such as EGF, FGF, PDGF, VEGF, and NGF. RTKs are transmembrane glycoproteins that are activated by the binding of their ligands, and they transduce the extracellular signal to the cytoplasm by phosphorylating tyrosine residues on the receptors themselves (autophosphorylation) and on downstream signaling proteins. RTKs activate numerous signaling pathways within cells, leading to cell proliferation, differentiation, migration, or metabolic changes. In addition, nonreceptor tyrosine kinases (NRTKs), which include Src, JAKs, and Abl, among others, are integral components of the signaling cascades triggered by RTKs and by other cell surface receptors such as GPCRs and receptors of the immune system. NRTKs are critical components in the regulation of the immune system.

RTKs and NRTKs have been implicated in the progression of diseases such as cancer, diabetic retinopathy, atherosclerosis, and psoriasis. Protein kinases, including RTKs, are one of the most frequently mutated gene families implicated in cancer, which has prompted numerous studies on their role in cancer pathogenesis. There are four main mechanisms of RTK dysregulation in human cancers: genomic rearrangements, autocrine activation, overexpression and gain- or loss-of-function mutations. Currently, there are several clinically available small molecule inhibitors and monoclonal antibodies against specific RTKs.

References:
[1] Hubbard SR, et al. Annu Rev Biochem. 2000;69:373-98.
[2] Robinson DR, et al. Oncogene. 2000 Nov 20;19(49):5548-57.
[3] McDonell LM, et al. Hum Mol Genet. 2015 Oct 15;24(R1):R60-6.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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Cell Cycle/DNA Damage >
Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
Cytoskeleton >
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Epigenetics >
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GPCR/G Protein >
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JAK/STAT Signaling >
EGFR JAK Pim STAT
MAPK/ERK Pathway >
ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
ATP Synthase BCRP Calcium Channel CFTR Chloride Channel CRAC Channel CRM1 EAAT2 GABA Receptor GlyT HCN Channel iGluR Monoamine Transporter Monocarboxylate Transporter Na+/Ca2+ Exchanger Na+/HCO3- Cotransporter Na+/K+ ATPase nAChR NKCC P-glycoprotein P2X Receptor Potassium Channel Proton Pump SGLT Sodium Channel TRP Channel URAT1
Metabolic Enzyme/Protease >
15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
PROTAC E3 Ligase Ligand-Linker Conjugate Ligand for E3 Ligase PROTAC Linker PROTAC-linker Conjugate for PAC
Protein Tyrosine Kinase/RTK >
Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
Stem Cell/Wnt >
Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
TGF-beta/Smad >
TGF-beta/Smad PKC ROCK TGF-β Receptor
Vitamin D Related >
VD/VDR
Others >
Androgen Receptor Aromatase Estrogen Receptor/ERR Progesterone Receptor Thyroid Hormone Receptor Others

Seribantumab

Seribantumab (MM 121) is a fully human IgG2 monoclonal antibody that targets HER3. Seribantumab blocks the activation of epidermal growth factor receptor (ErbB) family members and its downstream signal. Seribantumab inhibits neuregulin 1 (NRG1) fusion-dependent tumorigenesis in vitro and in vivo in breast, lung and ovarian patient-derived cancer models[1].

  • CAS Number: 1334296-12-6
  • MF:
  • MW: 143.2 (kDa)
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2784544

Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM.

  • CAS Number: 1229236-86-5
  • MF: C23H25ClFN7O
  • MW: 469.942
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SMAD3

SIS3 free base is a potent and selective inhibitor of TGF- beta1-induced Smad3 phosphorylation with an IC50 of 3 μM. SIS3 free base increases luciferase activity of p3TP-lux by abrogating the overexpression of constitutively active form of ALK-5[1].

  • CAS Number: 1009104-85-1
  • MF: C28H27N3O3
  • MW: 453.532
  • Catalog: ALK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 721.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 390.3±32.9 °C

ASN-002

ASN-002 is a potent dual inhibitor of spleen tyrosine kinase (SYK) and janus kinase (JAK) with IC50 values of 5-46 nM.

  • CAS Number: 1425381-60-7
  • MF: C24H28N8O2
  • MW: 460.53
  • Catalog: Syk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTK inhibitor 19

BTK inhibitor 19 is a highly selective, covalent BTK inhibitor (IC50 = 2.7 nM).

  • CAS Number: 2557174-19-1
  • MF: C25H24F3N7O3
  • MW: 527.50
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNK3 inhibitor-2

JNK3 inhibitor-2 is a potent and selective JNK3 inhibitor with IC50 values of >100, >100, 0.25 µM for JNK1, JNK2, JNK3, respectively. JNK3 inhibitor-2 shows DDR1 and EGFR (T790M, L858R) inhibition[1].

  • CAS Number: 2366264-18-6
  • MF: C20H14N2O2
  • MW: 314.34
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anti-inflammatory agent 21

Anti-inflammatory agent 21 (compound 9o) is an orally active and low cytotoxic anti-inflammatory agent, with an IC50 value of 0.76 μM for NO. Anti-inflammatory agent 21 acts via accumulation ROS and blocks the NF-κB/MAPK signaling pathway. Anti-inflammatory agent 21 can ameliorate cartilage destruction and inflammatory cell infiltration in arthritis rats model[1].

  • CAS Number: 2408836-40-6
  • MF: C24H21FO6
  • MW: 424.42
  • Catalog: NO Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-49

EGFR-IN-49 is a potent and selective EGFR inhibitor with IC50s of 65.0 nM and 13.6 nM for EGFRT790M and EGFRT790M/L858R, respectively. EGFR-IN-49 induces late apoptosis in a dose-dependent manner[1].

  • CAS Number: 2459932-81-9
  • MF: C22H15N5O2S
  • MW: 413.45
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMG-925

AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC50s of 2±1 nM and 3±1 nM, respectively.

  • CAS Number: 1401033-86-0
  • MF: C26H29N7O2
  • MW: 471.554
  • Catalog: FLT3
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 712.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.6±35.7 °C

SM 16

SM 16 is a ALK5/ALK4 kinase inhibitor with Kis of 10 and 1.5 nM, respectively.

  • CAS Number: 614749-78-9
  • MF: C25H26N4O3
  • MW: 430.5
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKI (5-24)

PKI(5-24) is a potent, competitive, and synthetic peptide inhibitor of PKA (cAMP-dependent protein kinase), with a Ki of 2.3 nM. PKI(5-24) corresponds to residues 5-24 in the naturally occurring heat-stable protein kinase inhibitor[1][2].

  • CAS Number: 99534-03-9
  • MF: C94H148N32O31
  • MW: 2222.38000
  • Catalog: PKA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-547632

CP-547632 is a potent inhibitor of the VEGFR2 and FGF2 kinases with IC50s of 11 and 9 nM, respectively.

  • CAS Number: 252003-65-9
  • MF: C20H24BrF2N5O3S
  • MW: 532.402
  • Catalog: VEGFR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 548.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.6±30.1 °C

ISCK03

ISCK03 is a specific SCF/c-Kit inhibitor.

  • CAS Number: 945526-43-2
  • MF: C19H21N3O2S
  • MW: 355.454
  • Catalog: c-Kit
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 520.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 268.3±32.9 °C

TIE-2/VEGFR-2 kinase-IN-3

TIE-2/VEGFR-2 kinase-IN-3, benzimidazole, is a potent TIE-2 and VEGFR-2 tyrosine kinase receptors inhibitors with IC50 values of 6.9 nM and 3.5 nM, respectively. TIE-2/VEGFR-2 kinase-IN-3 can be used for the research of angiogenesis[1].

  • CAS Number: 433224-09-0
  • MF: C23H17F4N5O3S
  • MW: 519.47
  • Catalog: VEGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zanubrutinib

Zanubrutinib is a selective Bruton tyrosine kinase (BTK) inhibitor.

  • CAS Number: 1691249-45-2
  • MF: C27H29N5O3
  • MW: 471.551
  • Catalog: Btk
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 713.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 385.2±32.9 °C

Fasudil

Fasudil is a potent inhibitor of ROCK1, PKA, PKC, and MLCK with Ki of 0.33 μM, 1.0 μM, 9.3 μM and 55 μM, respectively.

  • CAS Number: 103745-39-7
  • MF: C14H17N3O2S
  • MW: 291.37
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 506.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 259.9±32.9 °C

CEP-28122

CEP-28122 is a highly potent and selective orally active ALK inhibitor with IC50 of 1.9 ± 0.5 nM in an enzyme-based TRF assay.IC50 value: 1.9 ± 0.5 nMTarget: ALKin vitro: CEP-28122 is a potent inhibitor of recombinant ALK activity and cellular ALK tyrosine phosphorylation. CEP-28122 also inhibits Flt4 with IC50 of 46 ±10 nM. CEP-28122 induces concentration-dependent growth inhibition/cytotoxicity of ALK-positive anaplastic large-cell lymphoma (ALCL), non-small celllung cancer (NSCLC), and neuroblastoma cells. [1]in vivo: CEP-28122 displays dose-dependent inhibition of ALK tyrosine phosphorylation in tumor xenografts in mice, with substantial target inhibition (>90%) for more than12 hours following single oral dosing at 30 mg/kg. Dose-dependent antitumor activity was observed in ALK-positive ALCL, NSCLC, and neuroblastoma tumor xenografts in mice administered CEP-28122 orally, with complete/near complete tumor regressions observed following treatment at doses of 30 mg/kg twice daily or higher. [1]

  • CAS Number: 1022958-60-6
  • MF: C28H35ClN6O3
  • MW: 539.069
  • Catalog: ALK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 786.9±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 429.7±35.7 °C

Gliotoxin

Gliotoxin is a secondary metabolite, the most abundant mycotoxin secreted by A. fumigatus, inhibits the phagocytosis of macrophages and the immune functions of other immune cells [1]. Gliotoxin inhibits inducible NF-κB activity by preventing IκB degradation, which consequently induces host-cell apoptosis[2]. Gliotoxin activates PKA and increases intracellular cAMP concentration; modulates actin cytoskeleton rearrangement to facilitate A. fumigatus internalization into lung epithelial cells[3].

  • CAS Number: 67-99-2
  • MF: C13H14N2O4S2
  • MW: 326.391
  • Catalog: Apoptosis
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 699.7±55.0 °C at 760 mmHg
  • Melting Point: 153.5ºC
  • Flash Point: 377.0±31.5 °C

c-Fms-IN-1

c-Fms-IN-1 is a FMS kinase inhibitor with an IC50 of 0.0008 μM[1].

  • CAS Number: 885703-64-0
  • MF: C22H27N5O2
  • MW: 393.48
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GGTI-2147

GGTI-2147 is a potent GGTase I inhibitor. GGTI-2147 blocks geranyl-geranylation of Rap1A and reduces the activity of Rac1 (one of substrates for GGTI) and ameliorates the OGD/R-induced neuronal apoptosis.GGTI-2147 can be used for neurodevelopmental disorders research, such as autism, depression, and schizophrenia[1].

  • CAS Number: 191102-87-1
  • MF: C28H30N4O3
  • MW: 470.563
  • Catalog: ROS
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 710.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 383.5±32.9 °C

ALW-II-49-7

ALW-II-49-7 (DDR2-IN-1) is a potent, selective DDR2 inhibitor with IC50 of 18.6 nM, also shows ability to inhibit DDR1 and Ephrin-family kinases (IC50=40 nM for EphB2); displays excellent overall kinase selectivity against a panel of over 350 kinases; decreases DDR2 phosphorylation but has little effect on the proliferation of DDR2 mutated cancer cell lines.

  • CAS Number: 1135219-23-6
  • MF: C21H17F3N4O2
  • MW: 414.388
  • Catalog: Ephrin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SEL24-B489

SEL24-B489 (SEL24) is a potent, dual PIM and FLT3-ITD inhibitor with Kd of 2/2/3 nM for PIM1/2/3, Kd of 160/16 nM for FLT3-WT/FLT3-ITD, respectively; exhibits significantly broader on-target activity in AML cell lines (MV-4-11 GI50=20 nM) and primary AML blasts than selective FLT3-ITD or PIM inhibitors, decreases viability of AML cells with FLT3-TKD mutations associated with resistance to selective FLT3-ITD inhibitors; inhibits the growth of a broad panel of AML cell lines in xenograft models. Blood Cancer Phase 2 Clinical

  • CAS Number: 1616359-00-2
  • MF: C15H18Br2N4O2
  • MW: 446.143
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC2250

UNC2250 is a phosphorylation of endogenous Mer inhibitor with an IC50 of 9.8 nM and blocked ligand-stimulated activation of a chimeric EGFR-Mer protein.IC50 Value: 9.8 nM [1]Target: Othersin vitro: UNC2250 is 160-fold more active for Mer versus Axl and 60-fold versus Tyro3. UNC2250 had a moderate half-life, clearance, and volume of distribution as well as reasonable oral bioavailability and good solubility and was thus chosen for characterization of kinase selectivity and further evaluation in cell-based studies of Mer activity. UNC2250 efficiently inhibited ligand-dependent phosphorylation of a chimeric protein consisting of the extracellular and transmembrane domains of the epidermal growth factor (EGF) receptor and the intracellular tyrosine kinase domain of Mer. Moreover, UNC2250 incubation inhibited colony formation in soft agar cultures of the BT-12 rhabdoid tumor and the Colo699 NSCLC cell lines. In the Colo699 NSCLC cell line, the concentrations of UNC2250 required to inhibit colony formation and Mer phosphorylation were similar. These data suggest that the functional antiproliferative activity mediated by UNC2250 resulted from Mer inhibition rather than a consequence of off-target inhibition of other kinases [1,2].In vivo:

  • CAS Number: 1493694-70-4
  • MF: C24H36N6O2
  • MW: 440.582
  • Catalog: TAM Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 657.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 351.4±34.3 °C

LOXO-195 R racemate

(3aR)-Selitrectinib ((3aR)-LOXO-195) is an isform of Selitrectinib (HY-101977), which is a next-generation TRK kinase inhibitor, with IC50s of 0.6 nM and <2.5 nM for TRKA and TRKC, respectively[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Edecesertib

Edecesertib (GS-5718) is a selective, potent, orally active IRAK-4 inhibitor. Edecesertib has anti-inflammatory activity. Edecesertib can be used for rheumatoid arthritis (RA) and lupus erythematosus (LE) research[1][2].

  • CAS Number: 2408839-73-4
  • MF: C22H22FN7O2
  • MW: 435.45
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cevidoplenib dimesylate

Cevidoplenib is an orally available inhibitor of spleen tyrosine kinase (Syk), with potential anti-inflammatory and immunomodulating activities[1][2].

  • CAS Number: 2043659-93-2
  • MF: C27H35N7O9S2
  • MW: 665.74
  • Catalog: Syk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CE-245677

CE-245677 is a potent reversible inhibitor of Tie2 and TrkA/B kinases with a cellular IC50s of 4.7 and 1 nM.

  • CAS Number: 717899-97-3
  • MF: C24H22Cl2N6O3
  • MW: 513.38
  • Catalog: Trk Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FLT3-IN-1

FLT3-IN-1 is a potent FLT3 inhibitor extracted from patent WO2015056683A1, compound example A.

  • CAS Number: 1472797-69-5
  • MF: C29H38N8O2
  • MW: 530.66
  • Catalog: FLT3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CREBtide

CREBtide, a synthetic 13 amino acid peptide, has been reported as a PKA substrate.

  • CAS Number: 149155-45-3
  • MF: C73H129N29O19
  • MW: 1716.988
  • Catalog: Peptides
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trastuzumab beta

Trastuzumab beta (ABP 980) is a biosimilar to Trastuzumab (HY-P9907). Trastuzumab beta is a monoclonal antibody (McAb) targeting human epidermal growth factor receptor 2 (HER2). Trastuzumab beta can be used for the research of HER2-positive metastatic breast cancer, early breast cancer (EBC), and metastatic gastric cancer[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A