Simlukafusp Alfa Biosimilar Fusion Protein (FAP) for Research

Cat No.: GMP-Bios-INN-991

Pre-Made Simlukafusp Alfa Biosimilar, Fusion Protein targeting FAP fused with human IL2 (interleukin 2, IL-2): Recombinant therapeutic protein targeting DPPIV/FAPA/FAPalpha/SIMP is a biosimilar expressed by mammalian cell line as a benchmark reference therapeutic antibody for biological drug disovery items including cell culture, assay development, animal model development, PK/PD model development (Pharmacokinetics & Pharmacodynamic) and mechanism of action (MOA) research.

Simlukafusp alfa (SIM; FAP-IL2v) is an interleukin-2 variant moiety fused to a human antibody against fibroblast activation protein-α (FAP). Simlukafusp alfa bind to FAP expressed on cancer-associated fibroblasts and mediates its accumulation in malignant lesions. Simlukafusp alfa retains binding affinity to IL-2 receptor βγ without binding to IL-2Rα resulting in activation of immune effector NK and CD8 T cells but not regulatory T cells. FAP-IL2v is designed to increase the pool of activated immune effector cells and is intended to be a combination partner to enhance the efficacy of cancer immunotherapies.

Order Information

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Catalog No. Package Price(In USD)
GMP-Bios-INN-991-1mg 1mg 3090
GMP-Bios-INN-991-10mg 10mg
GMP-Bios-INN-991-100mg 100mg
GMP-Bios-INN-991-xmg ≥100mg



Product Details

Products Name (INN Index) Pre-Made Simlukafusp Alfa Biosimilar, Fusion Protein targeting FAP fused with human IL2 (interleukin 2, IL-2): Recombinant therapeutic protein targeting DPPIV/FAPA/FAPalpha/SIMP
INN Name Simlukafusp Alfa
TargetFAP
FormatFusion Protein
Derivationhuman
Species Reactivityhuman
CH1 IsotypeIgG1 - kappa
VD LCIgG1 - kappa
Highest_Clin_Trial (Jan '20)
Est. Status
100% SI Structure
99% SI Structure
95-98% SI Structure
Year Proposed
Year Recommended
CompaniesRoche, F. Hoffmann-La Roche Ltd. (Basel Switzerland)
Conditions Approved
Conditions Active
Conditions Discontinued
Development Tech0



About target - FAP

1. Protein Prolyl endopeptidase FAP

2. Gene FAP

3. Organism Homo sapiens (Human)

Function
Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble forms exhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2 (PubMed:14751930, PubMed:16223769, PubMed:16480718, PubMed:16410248, PubMed:17381073, PubMed:18095711, PubMed:21288888, PubMed:24371721).
Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vitronectin, tenascin, laminin, fibronectin, fibrin or casein (PubMed:9065413, PubMed:2172980, PubMed:7923219, PubMed:10347120, PubMed:10455171, PubMed:12376466, PubMed:16223769, PubMed:16651416, PubMed:18095711).
Also has dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro (PubMed:10347120, PubMed:10593948, PubMed:16175601, PubMed:16223769, PubMed:16651416, PubMed:16410248, PubMed:17381073, PubMed:21314817, PubMed:24371721, PubMed:24717288).
Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB) (PubMed:21314817).
The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner.

Catalytic activity
Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides. EC:3.4.21.26
Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline.
EC:3.4.14.5

Activity regulation
Gelatinase activity is inhibited by serine-protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF), 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF), 4-amidino phenylsulfonyl fluoride (APSF) and diisopropyl fluorophosphate (DFP), N-ethylmaleimide (NEM) and phenylmethylsulfonyl fluoride (PMSF). Dipeptidyl peptidase activity is inhibited by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), diisopropylfluorophosphate (DFP). Prolyl endopeptidase activity is inhibited by the boronic acid peptide Ac-Gly-BoroPro, Ac-Gly-Pro-chloromethyl ketone and Thr-Ser-Gly-chloromethyl ketone.

Kinetics
KM=0.46 mM for Ala-Pro (Dipeptidyl peptidase activity)
KM=0.9 mM for Lys-Pro (Dipeptidyl peptidase activity)
KM=1.15 mM for Gly-Pro (Dipeptidyl peptidase activity)
KM=0.25 mM for Gly-Pro (Dipeptidyl peptidase activity)
KM=0.24 mM for Ala-Pro (Dipeptidyl peptidase activity)
KM=0.10 mM for Ile-Pro (Dipeptidyl peptidase activity)
KM=0.24 mM for Phe-Pro (Dipeptidyl peptidase activity)
KM=0.24 mM for Gly-Pro (Dipeptidyl peptidase activity)
KM=0.33 mM for Ac-Gly-Pro (Prolyl endopeptidase activity)
KM=1.3 µM for Thr-Ser-Gly-Pro-Asn-Gln (Prolyl endopeptidase activity)
KM=2.2 µM for Ala-Ser-Gly-Pro-Asn-Gln (Prolyl endopeptidase activity)
KM=0.7 µM for Thr-Ala-Gly-Pro-Asn-Gln (Prolyl endopeptidase activity)
KM=1.9 µM for Thr-Ser-Gly-Pro-Ser-Gln (Prolyl endopeptidase activity)
KM=2.2 µM for Thr-Ser-Gly-Pro-Asn-Ser (Prolyl endopeptidase activity)
KM=4.3 µM for Ala-Ser-Gly-Pro-Ser-Ser (Prolyl endopeptidase activity)
KM=0.101 mM for Gly-Pro (FAP form, prolyl endopeptidase activity)
KM=0.124 mM for Gly-Pro (Antiplasmin-cleaving enzyme FAP soluble form, prolyl endopeptidase activity)
KM=0.323 mM for Gly-Pro (FAP form, dipeptidyl peptidase activity)
KM=0.272 mM for Gly-Pro (Antiplasmin-cleaving enzyme FAP soluble form, dipeptidyl peptidase activity)
KM=0.029 mM for Arg-Gly-Thr-Ser-Gly-Pro-Asn-Gln-Glu-Gln-Glu (FAP form, prolyl endopeptidase activity)
KM=0.026 mM for Arg-Gly-Thr-Ser-Gly-Pro-Asn-Gln-Glu-Gln-Glu (Antiplasmin-cleaving enzyme FAP soluble form, prolyl endopeptidase activity)
pH dependence
Optimum pH is 6-8.4 for gelatinase activity. At pH lower than 5 inhibited gelatinase activity.

Temperature dependence
Optimum temperature is 37 degrees Celsius for gelatinase activity. Temperatures above 50 degrees Celsius inhibit gelatinase activity.