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Notch Signalling Pathway
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ALX-270-415 Revised 14-Feb-07
Compound E
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SYNONYMS (2S)-2-{[(3,5-Difluorophenyl)acetyl]amino}-N-[(3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]propanamide
PRODUCT LINE Neurobiology
PRODUCT CATEGORY gamma-Secretase Protein Complex / Related Products
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-270-415-C250   250 µg 110.00 USD Add To Cart
ALX-270-415-M001   1 mg 285.00 USD Add To Cart
Product Specification
FORMULA: C27H24F2N4O3
MW: 490.5
PURITY: ≥98% (HPLC)
FORMULATION: White to off-white powder.
SOLUBILITY: Soluble in DMSO.
SHIPPING: AMBIENT
SHORT TERM STORAGE: +4°C
LONG TERM STORAGE: -20°C
HANDLING: Keep under inert gas.

Product Description
Cell permeable, potent, selective, non-transition state and non-competitive inhibitor of γ-secretase (IC50=0.3nM for total β-amyloid) and Notch processing. At higher concentrations (20-400µM), only weakly affects the presenilase activity. Activity tested!
Product Specific Literature References
Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors: D. Seiffert, et al.; J. Biol. Chem. 275, 34086 (2000) Abstract; Full Text
Pharmacological knock-down of the presenilin 1 heterodimer by a novel gamma -secretase inhibitor: implications for presenilin biology: D. Beher, et al.; J. Biol. Chem. 276, 45394 (2001) Abstract; Full Text
Presenilin-dependent gamma-secretase activity modulates thymocyte development: P. Doerfler, et al.; PNAS 98, 9312 (2001) Abstract; Full Text
gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase: C.Y. Ni, et al.; Science 294, 2179 (2001) Abstract
aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation: R. Francis, et al.; Dev. Cell 3, 85 (2002) Abstract
Presenilin-dependent gamma-secretase-like intramembrane cleavage of ErbB4: H.J. Lee, et al.; J. Biol. Chem. 277, 6318 (2002) Abstract; Full Text
Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines: G. Tian, et al.; J. Biol. Chem. 277, 31499 (2002) Abstract; Full Text
Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor: K.M. Jung, et al.; J. Biol. Chem. 278, 42161 (2003) Abstract; Full Text
Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44: D. Murakami, et al.; Oncogene 22, 1511 (2003) Abstract
Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria: C.A. Hansson, et al.; J. Biol. Chem. 279, 51654 (2004) Abstract; Full Text
Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia: A.P. Weng, et al.; Science 306, 269 (2004) Abstract
Identification of a new presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein: G. Zhao, et al.; J. Biol. Chem. 279, 50647 (2004) Abstract; Full Text
Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule: Z. Zou, et al.; J. Biol. Chem. 279, 34302 (2004) Abstract; Full Text
Determination of guinea-pig cortical gamma-secretase activity ex vivo following the systemic administration of a gamma-secretase inhibitor: S. Grimwood, et al.; Neuropharmacology 48, 1002 (2005) Abstract
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BACKGROUND/TECHNICAL INFORMATION Please also see our Product Flyer "Compound E - Cell-permeable, potent and selective γ-secretase inhibitor".
 
 
ALX-270-417 Revised 22-Oct-08
Compound 34
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SYNONYMS (2S,3R)-3-(3,4-Difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-2-oxo-5-phenyl-2,3-1H-benzo[e][1,4]diazepin-3-yl)butyramide
PRODUCT LINE Neurobiology
PRODUCT CATEGORY gamma-Secretase Protein Complex / Related Products
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-270-417-C200   200 µg 80.00 USD Add To Cart
ALX-270-417-M001   1 mg 240.00 USD Add To Cart
Product Specification
FORMULA: C31H24F3N3O3
MW: 543.5
PURITY: ≥98%
APPEARANCE: White to off-white powder.
SOLUBILITY: Soluble in DMSO.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
HANDLING: Protect from light. Hygroscopic.

Product Description
Cell permeable, highly potent inhibitor of γ-secretase (IC50=0.06nM).
Product Specific Literature References
Design and synthesis of highly potent benzodiazepine gamma-secretase inhibitors: preparation of (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4- hydroxy-N-((3S)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1H-benzo[e][1,4]-diazepin-3-yl)butyramide by use of a: I. Churcher, et al.; J. Med. Chem. 46, 2275 (2003) Abstract
 
 
ALX-260-127 Revised 01-Oct-07
γ-Secretase Inhibitor
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SYNONYMS MW167
PRODUCT LINE Neurobiology
PRODUCT CATEGORY gamma-Secretase Protein Complex / Related Products
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ALX-260-127-M001   1 mg 299.00 USD Add To Cart
ALX-260-127-M005   5 mg 1'321.00 USD Add To Cart
Product Specification
FORMULA: C33H57N5O9F2
MW: 705.8
PURITY: ≥90%
FORMULATION: Lyophilized.
SOLUBILITY: Soluble in DMSO containing 10% water.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
USE/STABILITY: Stock solutions in DMSO are stable for 6 months when stored at -20°C.
HANDLING: Protect from moisture.

Product Description
Reversible peptidomimetic inhibitor of γ-secretase (IC50=10-25µM for total β-amyloid), presenilinase (IC50=0.1-1µM), and calpain II (IC50=100µM).
Product Specific Literature References
Evidence that the 42- and 40-amino acid forms of amyloid beta protein are generated from the beta-amyloid precursor protein by different protease activities: M. Citron, et al.; PNAS 93, 13170 (1996) Abstract; Full Text
A substrate-based difluoro ketone selectively inhibits Alzheimer's gamma-secretase activity: M.S. Wolfe, et al.; J. Med. Chem. 41, 6 (1998) Abstract
Peptidomimetic probes and molecular modeling suggest that Alzheimer's gamma-secretase is an intramembrane-cleaving aspartyl protease: M.S. Wolfe, et al.; Biochemistry 38, 4720 (1999) Abstract
Presenilin endoproteolysis mediated by an aspartyl protease activity pharmacologically distinct from gamma-secretase: W.A. Campbell, et al.; J. Neurochem. 85, 1563 (2003) Abstract
 
 
ALX-201-382 Revised 24-Jul-08
DLL1 (human) (recombinant)
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SYNONYMS Delta-like Protein 1 (human) (recombinant)
Delta1 (human) (recombinant)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY Delta-like [DLL] & Jagged / Related Products
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-201-382-C010   10 µg 295.00 USD Add To Cart
ALX-201-382-C050   50 µg 795.00 USD Add To Cart
Product Specification
SOURCE/HOST: Produced in HEK 293 cells. Signal peptide and extracellular domain of recombinant human DLL1 (Delta-like protein 1; Delta1) (aa 1-545) is fused at the C-terminus to a FLAG®-tag.
CONCENTRATION:

PURITY: ≥90% (SDS-PAGE)
FORMULATION: Liquid. 0.2µm-filtered solution in PBS.
ENDOTOXIN CONTENT: <0.1EU/µg protein (LAL-test).
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
USE/STABILITY: Working aliquots are stable for up to 3 months when stored at -20°C.
HANDLING: After opening, prepare aliquots and store at -20°C. Avoid freeze/thaw cycles.
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General Information
Notch signalling pathways play key roles in cell-fate determination and differentiation in many tissues during embryonic and postnatal development. Notch ligands are divided into two subclasses, the delta and the serrate family [1]. Delta-like 1, 3, and 4 (DLL1, -3, -4), JAG1 and JAG2 with DSL (Delta, Serrate, Lag2) domain are typical Notch ligands, while DNER, F3/Contactin and NB-3 without DSL domain are atypical Notch ligands. Notch-ligand binding to NOTCH1, -2, -3, or -4 receptor induces the receptor proteolysis by metalloprotease and γ-secretase to release Notch intracellular domain (NICD).
DLL1 [1] is the human homolog of the Drosophila Notch ligand Delta [2]. Sequence analysis predicted that the 723-aa DLL1 transmembrane protein, which is 88% identical to the mouse DLL1 protein [3], has a DSL domain followed by 8 tandem EGF-like repeats and a short cytoplasmic C-terminal region. A soluble fusion protein containing the DSL domain of DLL1 and its adjacent 50 N-terminal aa inhibited the differentiation of myeloid progenitors but promoted their expansion [4]. DLL1 blocks the differentiation of progenitor cells into the B cell lineage while promoting the emergence of a population of cells with the characteristics of a T cell/NK cell precursor [5]. DLL1 undergoes proteolytic processing in its extracellular domain by ADAM10 and represents a substrate for several other members of the ADAM family [6, 7]. The soluble 38kDa Delta1 intracellular domain (DICD) that is generated by the presenilin-dependent γ-secretase cleavage is transported into the nucleus and likely plays a role in transcriptional events [8-10]. Recently it has been shown that DLL1 is essential for postnatal arteriogenesis [11].
BACKGROUND/TECHNICAL INFORMATION Swiss-Prot link O00548: DLL1 (human) [Precursor]

FLAG is a registered trademark of Sigma-Aldrich Co.
MANUFACTURER Manufactured by AdipoGen, Inc.
General Literature References
[1] Human ligands of the Notch receptor: G.E. Gray, et al.; Am. J. Pathol. 154, 785 (1999) Abstract; Full Text
[2] The molecular genetics of early neurogenesis in Drosophila melanogaster: E. Knust and J.A. Campos-Ortega; Bioessays 11, 95 (1989) Abstract
[3] Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta: B. Bettenhausen, et al.; Development 121, 2407 (1995) Abstract; Full Text
[4] A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells: W. Han, et al.; Blood 95, 1616 (2000) Abstract; Full Text
[5] Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation: A.C. Jaleco, et al.; J. Exp. Med. 194, 991 (2001) Abstract; Full Text
[6] The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase: E. Six, et al.; PNAS 100, 7638 (2003) Abstract; Full Text
[7] Proteolytic processing of delta-like 1 by ADAM proteases: E. Dyczynska, et al.; J. Biol. Chem. 282, 436 (2007) Abstract; Full Text
[8] Notch-induced proteolysis and nuclear localization of the Delta ligand: C.E. Bland, et al.; J. Biol. Chem. 278, 13607 (2003) Abstract; Full Text
[9] The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage: T. Ikeuchi and S.S. Sisodia; J. Biol. Chem. 278, 7751 (2003) Abstract; Full Text
[10] The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments: M.J. LaVoie and D.J. Selkoe; J. Biol. Chem. 278, 34427 (2003) Abstract; Full Text
[11] The Notch Ligand Delta-Like 1 is Essential for Postnatal Arteriogenesis: A. Limbourg, et al.; Circ. Res. 100, 363 (2007) Abstract
[12] NOTCH signaling as a novel cancer therapeutic target: L. Miele, et al.; Curr. Cancer Drug Targets 6, 313 (2006) Abstract
[13] Notch signaling in gastrointestinal tract: M. Katoh; Int. J. Oncol. 30, 247 (2007), Review Abstract
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Recombinant Proteins / Fusion Proteins
 
 
ALX-201-386 Revised 26-May-08
DLL4 (human):Fc (human) (recombinant)
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SYNONYMS Delta-like Protein 4 (human):Fc (human) (recombinant)
Delta4 (human):Fc (human) (recombinant)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY Delta-like [DLL] & Jagged / Related Products
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-201-386-C010   10 µg 310.00 USD Add To Cart
ALX-201-386-C050   50 µg 860.00 USD Add To Cart
Product Specification
SOURCE/HOST: Produced in HEK 293 cells. Signal peptide and extracellular domain of recombinant human DLL4 (Delta-like protein 4; Delta4) (aa 1-529) is fused at the C-terminus to the Fc portion of human IgG1.
CONCENTRATION:

PURITY: ≥90% (SDS-PAGE)
FORMULATION: Liquid. 0.2µm-filtered solution in PBS.
ENDOTOXIN CONTENT: <0.1EU/µg protein (LAL-test).
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
USE/STABILITY: Working aliquots are stable for up to 3 months when stored at -20°C.
HANDLING: After opening, prepare aliquots and store at -20°C. Avoid freeze/thaw cycles.
Product Images
Please click on thumbnails to enlarge.
General Information
Notch signalling pathways play key roles in cell-fate determination and differentiation in many tissues during embryonic and postnatal development. Notch ligands are divided into two subclasses, the delta and the serrate family [1]. DLL4 (Dll4) is a novel delta family member and exhibits all the hallmarks of the delta family of Notch ligands [2]. Human DLL4 shares 86% aa sequence identity with mouse Dll4. The extracellular region of the 685 aa protein contains 8 EGF-like repeats as well as a DSL (Delta, Serrate, Lag2) domain necessary for receptor binding. The protein also contains a transmembrane domain and a cytoplasmic tail lacking any catalytic motifs. DLL4 is largely restricted to the vascular endothelium and has been shown to function as a ligand for Notch1 and Notch4 [3]. Signalling through Notch1 regulates formation of tip cells during angiogenesis [4].
BACKGROUND/TECHNICAL INFORMATION Swiss-Prot link Q9NR61: DLL4 (human) [Precursor]
MANUFACTURER Manufactured by AdipoGen, Inc.
General Literature References
[1] Human ligands of the Notch receptor: G.E. Gray, et al.; Am. J. Pathol. 154, 785 (1999) Abstract
[2] Dll4, a novel Notch ligand expressed in arterial endothelium: J.R. Shutter, et al.; Genes Dev. 14, 1313 (2000) Abstract
[3] Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting: I.B. Lobov, et al.; PNAS 104, 3219 (2007) Abstract
[4] Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis: M. Hellstrom, et al.; Nature 445, 776 (2007) Abstract
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Recombinant Proteins / Fusion Proteins
 
 
ALX-201-390 Revised 27-Aug-08
Jagged-1 (human):Fc (human) (recombinant)
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SYNONYMS HJ1 (human):Fc (human) (recombinant)
CD339 (human):Fc (human) (recombinant)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY Delta-like [DLL] & Jagged / Related Products
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-201-390-C010   10 µg 295.00 USD Add To Cart
ALX-201-390-C050   50 µg 660.00 USD Add To Cart
Product Specification
SOURCE/HOST: Produced in HEK 293 cells. Signal peptide and extracellular domain of human Jagged-1 (HJ1; CD339) (aa 1-1067) are fused at the C-terminus to the Fc portion of human IgG.
CONCENTRATION: 0.5mg/ml
PURITY: ≥90% (SDS-PAGE)
FORMULATION: Liquid. 0.2µm-filtered solution in PBS.
ENDOTOXIN CONTENT: <0.1EU/µg protein (LAL-test).
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
USE/STABILITY: Working aliquots are stable for up to 3 months when stored at -20°C.
HANDLING: Avoid freeze/thaw cycles. After opening, prepare aliquots and store at -20°C.
Product Images
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General Information

The Notch family of proteins are involved in the regulation of key biological processes such as cell fate determination, proliferation, differentiation, and apoptosis. Jagged-1 (HJ1; CD339), a cell surface glycoprotein, is one of several ligands that activate multiple Notch receptors  and is involved in mediating Notch signalling. Jagged-1 signalling through Notch has been shown to play a role in hematopoiesis. Jagged-1 also seems to be involved in early and late stages of mammalian cardiovascular development. It has been shown to enhance fibroblast growth factor-induced angiogenesis (in vitro). Mutations in the human Jagged-1 gene cause Alagille syndrome.
Jagged-1 binds to Notch 1 receptors and activates Notch 1-dependent signalling pathways. For example, Jagged-1 inhibits T cell activation and is a promising therapeutically beneficial protein for multiple sclerosis or other autoimmune diseases. Additionally Jagged-1 was shown to block osteoclastogenesis in the presence of RANKL and M-CSF.
BACKGROUND/TECHNICAL INFORMATION Swiss-Prot link P78504: Jagged-1 [Precursor]
MANUFACTURER Manufactured by AdipoGen, Inc.
General Literature References
An antisense oligonucleotide to the notch ligand jagged enhances fibroblast growth factor-induced angiogenesis in vitro: A.B. Zimrin. et al.; J. Biol. Chem. 271, 32499 (1996) Abstract; Full Text
Mutations in the human Jagged1 gene are responsible for Alagille syndrome: T. Oda, et al.; Nat. Genet. 16, 235 (1997) Abstract
Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation: B.W. Purow, et al.; Cancer Res. 65, 2353 (2005) Abstract; Full Text
Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes: H. Li, et al.; BBRC 341, 320 (2006) Abstract
Up-regulation of gene related to anergy in lymphocytes is associated with Notch-mediated human T cell suppression: A.M. Kostianovsky, et al.; J. Immunol. 178, 6158 (2007) Abstract; Full Text
Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development: F.A. High, et al.; PNAS 105, 1955 (2008) Abstract
NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells: S. Bai, et al.; J. Biol. Chem. 283, 6509 (2008) Abstract; Full Text
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Recombinant Proteins / Fusion Proteins • Angiogenesis Other Products
 
 
ALX-201-416 Revised 09-Jul-08
Dlk1 (mouse):Fc (human) (recombinant)
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SYNONYMS Delta-like Protein (DLK) (mouse):Fc (human) (recombinant)
Pref-1 (mouse):Fc (human) (recombinant)
Preadipocyte Factor 1 (mouse):Fc (human) (recombinant)
Fetal Antigen 1 (FA1) (mouse):Fc (human) (recombinant)
PRODUCT LINE Obesity & Adipokines
PRODUCT CATEGORY Adipokines Other Products
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Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-201-416-C010   10 µg 250.00 USD Add To Cart
ALX-201-416-C050   50 µg 570.00 USD Add To Cart
Product Specification
SOURCE/HOST: Produced in HEK 293 cells. The signal peptide and the extracellular domain of mouse Dlk1 (aa 1-305) is fused at the C-terminus to the Fc portion of human IgG.
PURITY: ≥90% (SDS-PAGE)
FORMULATION: Liquid. 0.2µm-filtered solution in PBS.
ENDOTOXIN CONTENT: <1EU/µg protein (LAL-test).
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: -20°C
HANDLING: Avoid freeze/thaw cycles. After opening, prepare aliquots and store at -20°C.
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General Information
BACKGROUND/TECHNICAL INFORMATION Swiss-Prot link Q09163: DLK (mouse)
MANUFACTURER Manufactured by AdipoGen, Inc.
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Further Categories Containing This Product:
Recombinant Proteins / Fusion Proteins • Delta-like [DLL] & Jagged / Related Products • Cell Differentiation
 
 
ALX-201-422 Revised 09-Jun-08 New product
DLL3 (human):Fc (human) (recombinant)
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SYNONYMS Delta-like Protein 3 (human):Fc (human) (recombinant)
Delta3 (human):Fc (human) (recombinant)
PRODUCT LINE Signal Transduction
PRODUCT CATEGORY Delta-like [DLL] & Jagged / Related Products
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ALX-201-422-C010   10 µg 300.00 USD Add To Cart
ALX-201-422-C050   50 µg 830.00 USD Add To Cart
Product Specification
SOURCE/HOST: Produced in HEK 293 cells. Signal peptide and extracellular domain of recombinant human DLL3 (aa 1-466) is fused at the C-terminus to the Fc portion of human IgG1.
PURITY: ≥90% (SDS-PAGE)
FORMULATION: Liquid. 0.2µm-filtered solution in PBS.
ENDOTOXIN CONTENT: <0.1EU/µg protein (LAL-test).
SHIPPING: SHIPPED ON BLUE ICE
LONG TERM STORAGE: