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210344-98-2,MFCD03490491
Catalog No.:AA002KM7

210344-98-2 | Z-IETD-FMK

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1mg
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  • Technical Information
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Technical Information
Catalog Number:
AA002KM7
Chemical Name:
Z-IETD-FMK
CAS Number:
210344-98-2
Molecular Formula:
C30H43FN4O11
Molecular Weight:
654.6810
MDL Number:
MFCD03490491
SMILES:
COC(=O)CCC(C(=O)NC(C(=O)NC(C(=O)CF)CC(=O)OC)C(O)C)NC(=O)C(C(CC)C)NC(=O)OCc1ccccc1
Properties
Computed Properties
 
Complexity:
1050  
Covalently-Bonded Unit Count:
1  
Defined Atom Stereocenter Count:
6  
Heavy Atom Count:
46  
Hydrogen Bond Acceptor Count:
12  
Hydrogen Bond Donor Count:
5  
Rotatable Bond Count:
22  
XLogP3:
1.2  

Literature

Title: Molecular mechanism and inhibitory targets of dioscin in HepG2 cells.

Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 20181001

Title: Nickel ions from a corroded cardiovascular stent induce monocytic cell apoptosis: Proposed impact on vascular remodeling and mechanism.

Journal: Journal of the Formosan Medical Association = Taiwan yi zhi 20151101

Title: Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement.

Journal: American journal of physiology. Heart and circulatory physiology 20140601

Title: Iso-suillin from the mushroom Suillus flavus induces cell cycle arrest and apoptosis in K562 cell line.

Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 20140501

Title: Quercetin-3-O-(2'-galloyl)-α-l-rhamnopyranoside prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway.

Journal: Chemico-biological interactions 20130825

Title: Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling.

Journal: Toxicology and applied pharmacology 20130601

Title: Zebularine inhibits the growth of HeLa cervical cancer cells via cell cycle arrest and caspase-dependent apoptosis.

Journal: Molecular biology reports 20121001

Title: Multi-walled carbon nanotubes induce apoptosis via mitochondrial pathway and scavenger receptor.

Journal: Toxicology in vitro : an international journal published in association with BIBRA 20120901

Title: Docosahexaenoic acid sensitizes colon cancer cells to sulindac sulfide-induced apoptosis.

Journal: Oncology reports 20120601

Title: 5-Phenylselenyl- and 5-methylselenyl-methyl-2'-deoxyuridine induce oxidative stress, DNA damage, and caspase-2-dependent apoptosis in cancer cells.

Journal: Apoptosis : an international journal on programmed cell death 20120201

Title: The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells.

Journal: Toxicology in vitro : an international journal published in association with BIBRA 20120201

Title: J7, a methyl jasmonate derivative, enhances TRAIL-mediated apoptosis through up-regulation of reactive oxygen species generation in human hepatoma HepG2 cells.

Journal: Toxicology in vitro : an international journal published in association with BIBRA 20120201

Title: Dehydrocorydaline inhibits breast cancer cells proliferation by inducing apoptosis in MCF-7 cells.

Journal: The American journal of Chinese medicine 20120101

Title: Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-Bid mitochondrial pathway.

Journal: Journal of Asian natural products research 20120101

Title: Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: a role of combined treatment versus monotherapy.

Journal: Apoptosis : an international journal on programmed cell death 20111201

Title: Okadaic acid induces apoptosis through the PKR, NF-κB and caspase pathway in human osteoblastic osteosarcoma MG63 cells.

Journal: Toxicology in vitro : an international journal published in association with BIBRA 20111201

Title: Characterization of Cholix toxin-induced apoptosis in HeLa cells.

Journal: The Journal of biological chemistry 20111028

Title: Combined inhibition of DNA methyltransferase and histone deacetylase restores caspase-8 expression and sensitizes SCLC cells to TRAIL.

Journal: Carcinogenesis 20111001

Title: Silibinin triggers apoptotic signaling pathways and autophagic survival response in human colon adenocarcinoma cells and their derived metastatic cells.

Journal: Apoptosis : an international journal on programmed cell death 20111001

Title: Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics.

Journal: PLoS computational biology 20111001

Title: The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells.

Journal: Neurochemistry international 20110801

Title: Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells.

Journal: Carcinogenesis 20110501

Title: Amiodarone sensitizes human glioma cells but not astrocytes to TRAIL-induced apoptosis via CHOP-mediated DR5 upregulation.

Journal: Neuro-oncology 20110301

Title: Sequential caspase-2 and caspase-8 activation is essential for saikosaponin a-induced apoptosis of human colon carcinoma cell lines.

Journal: Apoptosis : an international journal on programmed cell death 20110201

Title: 3,3'-Diindolylmethane inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model.

Journal: Molecular carcinogenesis 20110201

Title: Combined treatment with the Cox-2 inhibitor niflumic acid and PPARγ ligand ciglitazone induces ER stress/caspase-8-mediated apoptosis in human lung cancer cells.

Journal: Cancer letters 20110128

Title: Danthron, an anthraquinone derivative, induces DNA damage and caspase cascades-mediated apoptosis in SNU-1 human gastric cancer cells through mitochondrial permeability transition pores and Bax-triggered pathways.

Journal: Chemical research in toxicology 20110114

Title: Glucocorticoid-induced activation of caspase-8 protects the glucocorticoid-induced protein Gilz from proteasomal degradation and induces its binding to SUMO-1 in murine thymocytes.

Journal: Cell death and differentiation 20110101

Title: Caspase activation is not required for villous cytotrophoblast fusion into syncytiotrophoblasts.

Journal: Placenta 20101101

Title: 1-(3',4',5'-Trimethoxyphenyl)-3-(3'',4''-dimethoxy-2''-hydroxyphenyl)-propane with microtubule-depolymerizing ability induces G2/M phase arrest and apoptosis in HepG2 cells.

Journal: Chemico-biological interactions 20101006

Title: Isoangustone A present in hexane/ethanol extract of Glycyrrhiza uralensis induces apoptosis in DU145 human prostate cancer cells via the activation of DR4 and intrinsic apoptosis pathway.

Journal: Molecular nutrition & food research 20100901

Title: Distinct combinatorial effects of the plant polyphenols curcumin, carnosic acid, and silibinin on proliferation and apoptosis in acute myeloid leukemia cells.

Journal: Nutrition and cancer 20100801

Title: Methyl antcinate A from Antrodia camphorata induces apoptosis in human liver cancer cells through oxidant-mediated cofilin- and Bax-triggered mitochondrial pathway.

Journal: Chemical research in toxicology 20100719

Title: Caspases-2 and -8 are involved in the presenilin1/gamma-secretase-dependent cleavage of amyloid precursor protein after the induction of apoptosis.

Journal: Journal of neuroscience research 20100701

Title: Para-phenylenediamine induced DNA damage and apoptosis through oxidative stress and enhanced caspase-8 and -9 activities in Mardin-Darby canine kidney cells.

Journal: Toxicology in vitro : an international journal published in association with BIBRA 20100601

Title: Sulfur mustard induces apoptosis in lung epithelial cells via a caspase amplification loop.

Journal: Toxicology 20100527

Title: The Ca(2+) channel blocker flunarizine induces caspase-10-dependent apoptosis in Jurkat T-leukemia cells.

Journal: Apoptosis : an international journal on programmed cell death 20100501

Title: Ursodeoxycholic acid switches oxaliplatin-induced necrosis to apoptosis by inhibiting reactive oxygen species production and activating p53-caspase 8 pathway in HepG2 hepatocellular carcinoma.

Journal: International journal of cancer 20100401

Title: Celecoxib-induced apoptosis is enhanced by ABT-737 and by inhibition of autophagy in human colorectal cancer cells.

Journal: Autophagy 20100201

Title: Role of endoplasmic reticulum stress in alpha-TEA mediated TRAIL/DR5 death receptor dependent apoptosis.

Journal: PloS one 20100101

Title: Sulphasalazine accelerates apoptosis in neutrophils exposed to immune complex: Role of caspase pathway.

Journal: Clinical and experimental pharmacology & physiology 20091101

Title: Recombinant YopJ induces apoptosis in murine peritoneal macrophages in vitro: involvement of mitochondrial death pathway.

Journal: International immunology 20091101

Title: Involvement of mitochondria and recruitment of Fas/CD95 signaling in lipid rafts in resveratrol-mediated antimyeloma and antileukemia actions.

Journal: Oncogene 20090910

Title: Titanium dioxide nanoparticles induce apoptosis through the JNK/p38-caspase-8-Bid pathway in phytohemagglutinin-stimulated human lymphocytes.

Journal: Biochemical and biophysical research communications 20090904

Title: The anti-apoptotic effects of caspase inhibitors on propyl gallate-treated HeLa cells in relation to reactive oxygen species and glutathione levels.

Journal: Archives of toxicology 20090901

Title: Cyclic stretching force induces apoptosis in human periodontal ligament cells via caspase-9.

Journal: Archives of oral biology 20090901

Title: N,N-dimethyl phytosphingosine induces caspase-8-dependent cytochrome c release and apoptosis through ROS generation in human leukemia cells.

Journal: Toxicology and applied pharmacology 20090815

Title: Mechanisms of resveratrol-induced platelet apoptosis.

Journal: Cardiovascular research 20090801

Title: Involvement of both extrinsic and intrinsic apoptotic pathways in apoptosis induced by genistein in human cervical cancer cells.

Journal: Annals of the New York Academy of Sciences 20090801

Title: Genistein enhances TRAIL-induced apoptosis through inhibition of p38 MAPK signaling in human hepatocellular carcinoma Hep3B cells.

Journal: Chemico-biological interactions 20090715

Title: Nimesulide, a selective COX-2 inhibitor, acts synergistically with ionizing radiation against A549 human lung cancer cells through the activation of caspase-8 and caspase-3.

Journal: International journal of oncology 20090501

Title: Caspase-8 is involved in neovascularization-promoting progenitor cell functions.

Journal: Arteriosclerosis, thrombosis, and vascular biology 20090401

Title: Multiple signal transduction pathways in okadaic acid induced apoptosis in HeLa cells.

Journal: Toxicology 20090204

Title: Caspase-dependent molecular mechanisms of anti-human DR5 monoclonal antibody mDRA-6 inducing apoptosis of human leukemia Jurkat cells.

Journal: Ai zheng = Aizheng = Chinese journal of cancer 20090201

Title: Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism.

Journal: Nutrition and cancer 20090101

Title: Protein tyrosine kinase p56lck-deficiency confers hypersusceptibility to rho-fluorophenylalanine (pFPhe)-induced apoptosis by augmenting mitochondrial apoptotic pathway in human Jurkat T cells.

Journal: Biochemical and biophysical research communications 20081205

Title: Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8-mediated Bid cleavage.

Journal: Molecular cancer therapeutics 20080601

Title: The characteristic of an anti-human DR5 antibody A6.

Journal: Cellular & molecular immunology 20080601

Title: Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes.

Journal: Histochemistry and cell biology 20080501

Title: Bid is not required for Bax translocation during UV-induced apoptosis.

Journal: Cellular signalling 20071201

Title: Synapse-specific plasticity in command neurons during learning of edible snails under the action of caspase inhibitors.

Journal: Bulletin of experimental biology and medicine 20071201

Title: Arsenic trioxide sensitizes promonocytic leukemia cells to TNFalpha-induced apoptosis via p38-MAPK-regulated activation of both receptor-mediated and mitochondrial pathways.

Journal: Biochimica et biophysica acta 20071101

Title: Acacetin-induced apoptosis of human breast cancer MCF-7 cells involves caspase cascade, mitochondria-mediated death signaling and SAPK/JNK1/2-c-Jun activation.

Journal: Molecules and cells 20070831

Title: Cytotoxicity of diacetoxyscirpenol is associated with apoptosis by activation of caspase-8 and interruption of cell cycle progression by down-regulation of cdk4 and cyclin B1 in human Jurkat T cells.

Journal: Toxicology and applied pharmacology 20070715

Title: TNFalpha induces apoptosis through JNK/Bax-dependent pathway in differentiated, but not naïve PC12 cells.

Journal: Cell cycle (Georgetown, Tex.) 20070615

Title: Activation of the death receptor pathway of apoptosis by the aldehyde acrolein.

Journal: Free radical biology & medicine 20070315

Title: Sulfasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas.

Journal: International journal of oncology 20070101

Title: Activation of caspase-8 triggers anoikis in human neuroblastoma cells.

Journal: Neuroscience research 20061001

Title: Proline oxidase activates both intrinsic and extrinsic pathways for apoptosis: the role of ROS/superoxides, NFAT and MEK/ERK signaling.

Journal: Oncogene 20060914

Title: Re-evaluation of the distinction between type I and type II cells: the necessary role of the mitochondria in both the extrinsic and intrinsic signaling pathways upon Fas receptor activation.

Journal: Journal of cellular physiology 20060901

Title: Inhibition of caspase-8 attenuates neuronal death induced by limbic seizures in a cytochrome c-dependent and Smac/DIABLO-independent way.

Journal: Brain research 20060707

Title: Cadmium-induced apoptosis in murine macrophages is antagonized by antioxidants and caspase inhibitors.

Journal: Journal of toxicology and environmental health. Part A 20060601

Title: Interaction between endoplasmic reticulum stress and caspase 8 activation in retrovirus MoMuLV-ts1-infected astrocytes.

Journal: Virology 20060510

Title: Cadmium inhibits both intrinsic and extrinsic apoptotic pathways in renal mesangial cells.

Journal: American journal of physiology. Renal physiology 20060501

Title: Prostate-apoptosis-response-gene-4 increases sensitivity to TRAIL-induced apoptosis.

Journal: Leukemia research 20060501

Title: E-cadherin and its downstream catenins are proteolytically cleaved in human HaCaT keratinocytes exposed to UVB.

Journal: Experimental dermatology 20060401

Title: Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of beta-amyloid on rat brain microvascular endothelial cells.

Journal: International journal of molecular medicine 20060301

Title: Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR5 upregulation and caspase 8-dependent pathway.

Journal: Cancer biology & therapy 20060201

Title: Apo2L/TRAIL is an indirect mediator of apoptosis induced by interferon-alpha in human myeloma cells.

Journal: FEBS letters 20051107

Title: Synergistic apoptosis induction by proteasome and histone deacetylase inhibitors is dependent on protein synthesis.

Journal: Apoptosis : an international journal on programmed cell death 20050801

Title: Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium.

Journal: The Biochemical journal 20050715

Title: Tumor necrosis factor-{alpha} decreases Akt protein levels in 3T3-L1 adipocytes via the caspase-dependent ubiquitination of Akt.

Journal: Endocrinology 20050601

Title: Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines.

Journal: Molecular cancer therapeutics 20050401

Title: Boswellic acid acetate induces apoptosis through caspase-mediated pathways in myeloid leukemia cells.

Journal: Molecular cancer therapeutics 20050301

Title: CD95 apoptosis resistance in certain cells can be overcome by noncanonical activation of caspase-8.

Journal: Cell death and differentiation 20050101

Title: Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells.

Journal: British journal of cancer 20041101

Title: FLIP overexpression inhibits death receptor-induced apoptosis in malignant mesothelial cells.

Journal: Oncogene 20041014

Title: Lovastatin inhibits tumor growth and lung metastasis in mouse mammary carcinoma model: a p53-independent mitochondrial-mediated apoptotic mechanism.

Journal: Carcinogenesis 20041001

Title: Molecular mechanisms of TNF-alpha-induced ceramide formation in human glioma cells: P53-mediated oxidant stress-dependent and -independent pathways.

Journal: Cell death and differentiation 20040901

Title: 6-Hydroxydopamine induces dopaminergic cell degeneration via a caspase-9-mediated apoptotic pathway that is attenuated by caspase-9dn expression.

Journal: Journal of neuroscience research 20040901

Title: Role of glutathione in dimethylarsinic acid-induced apoptosis.

Journal: Toxicology and applied pharmacology 20040801

Title: Ca influx shutdown in neutrophils induced by Fas (CD95) cross-linking.

Journal: Immunology 20040701

Title: Norepinephrine induces apoptosis in neonatal rat cardiomyocytes through a reactive oxygen species-TNF alpha-caspase signaling pathway.

Journal: Cardiovascular research 20040601

Title: Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury.

Journal: American journal of physiology. Heart and circulatory physiology 20040501

Title: Caspase inhibitors attenuate superantigen-induced inflammatory cytokines, chemokines, and T-cell proliferation.

Journal: Clinical and diagnostic laboratory immunology 20040501

Title: Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase.

Journal: Biochemical and biophysical research communications 20040312

Title: Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines.

Journal: British journal of haematology 20031201

Title: Resveratrol-induced apoptosis is associated with Fas redistribution in the rafts and the formation of a death-inducing signaling complex in colon cancer cells.

Journal: The Journal of biological chemistry 20031017

Title: Influenza A virus-induced apoptosis in bronchiolar epithelial (NCI-H292) cells limits pro-inflammatory cytokine release.

Journal: The Journal of general virology 20030901

Title: Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells.

Journal: Molecular cancer therapeutics 20030901

Title: Anti-angiogenesis effects of borrelidin are mediated through distinct pathways: threonyl-tRNA synthetase and caspases are independently involved in suppression of proliferation and induction of apoptosis in endothelial cells.

Journal: The Journal of antibiotics 20030801

Title: Paraoxon induces apoptosis in EL4 cells via activation of mitochondrial pathways.

Journal: Toxicology and applied pharmacology 20030701

Title: New benzo(b)thiophenesulphonamide 1,1-dioxide derivatives induce a reactive oxygen species-mediated process of apoptosis in tumour cells.

Journal: Oncogene 20030612

Title: Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loop.

Journal: Oncogene 20030417

Title: Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway.

Journal: Journal of immunology (Baltimore, Md. : 1950) 20030401

Title: Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341.

Journal: Blood 20030215

Title: Study of caspase inhibitors for limiting death in mammalian cell culture.

Journal: Biotechnology and bioengineering 20030205

Title: Neutralization of TRAIL death pathway protects human neuronal cell line from beta-amyloid toxicity.

Journal: Cell death and differentiation 20030101

Title: Mitomycin C induces apoptosis and caspase-8 and -9 processing through a caspase-3 and Fas-independent pathway.

Journal: Cell death and differentiation 20020901

Title: DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way.

Journal: Oncogene 20020829

Title: Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells.

Journal: Acta pharmacologica Sinica 20020401

Title: Acid sphingomyelinase activation requires caspase-8 but not p53 nor reactive oxygen species during Fas-induced apoptosis in human glioma cells.

Journal: Experimental cell research 20020215

Title: Involvement of caspases and of mitochondria in Fas ligation-induced eosinophil apoptosis: modulation by interleukin-5 and interferon-gamma.

Journal: Journal of leukocyte biology 20011101

Title: Differential involvement of initiator caspases in apoptotic volume decrease and potassium efflux during Fas- and UV-induced cell death.

Journal: The Journal of biological chemistry 20011005

Title: Cleavage of bid may amplify caspase-8-induced neuronal death following focally evoked limbic seizures.

Journal: Neurobiology of disease 20010801

Title: beta-amyloid induces caspase-dependent early neurotoxic change in PC12 cells: correlation with H2O2 neurotoxicity.

Journal: Neuroscience letters 20010601

Title: Treatment with inhibitors of caspases, that are substrates of drug transporters, selectively permits chemotherapy-induced apoptosis in multidrug-resistant cells but protects normal cells.

Journal: Leukemia 20010601

Title: Oxyhemoglobin induces caspase-mediated cell death in cerebral endothelial cells.

Journal: Journal of neurochemistry 20010501

Title: Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8.

Journal: FEBS letters 20010323

Title: Signaling events triggered by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): caspase-8 is required for TRAIL-induced apoptosis.

Journal: Cancer research 20010201

Title: Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels.

Journal: Cancer research 20010115

Title: Apoptosis induced by cadmium in human lymphoma U937 cells through Ca2+-calpain and caspase-mitochondria- dependent pathways.

Journal: The Journal of biological chemistry 20001215

Title: Studies on the mechanism of the inhibition of human leukaemia cell growth by dietary isothiocyanates and their cysteine adducts in vitro.

Journal: Biochemical pharmacology 20000715

Title: Cytochrome c-dependent activation of caspase-3 by tumor necrosis factor requires induction of the mitochondrial permeability transition.

Journal: The American journal of pathology 20000601

Title: Rapid nucleolytic degradation of the small cytoplasmic Y RNAs during apoptosis.

Journal: The Journal of biological chemistry 19990827

Title: Cowburn AS, et al. z-VAD-fmk augmentation of TNF alpha-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species.

Title: Lawrence CP, et al. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties. Toxicol Appl Pharmacol. 2012 Nov 15;265(1):103-12.

Title: Tezel G, et al. Inhibition of caspase activity in retinal cell apoptosis induced by various stimuli in vitro. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2660-7.

Title: Terlizzi M, et al. Pharmacological inhibition of caspase-8 limits lung tumour outgrowth. Br J Pharmacol. 2015 Aug;172(15):3917-28.

Title: Yang J, et al. Granzyme B Is an Essential Mediator in CD8+ T Cell Killing of Theileria parva-Infected Cells.Infect Immun. 2018 Dec 19;87(1). pii: e00386-18.

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Tags:210344-98-2 Molecular Formula|210344-98-2 MDL|210344-98-2 SMILES|210344-98-2 Z-IETD-FMK