==== Reference: Usmani SS, Bedi G, Samuel JS, Singh S, Kalra S, Kumar P, et al. (2017) THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS ONE 12(7) e0181748.====

Detailed description page of THPdb


Details of Th1174 which contains 2 entries.


Entry 1
(1) Primary information
ID1723
ThPP IDTh1174
Therapeutic Peptide/Protein NameDaratumumab
SequenceNA view full sequnce in fasta
Functional ClassificationIIIc
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting Point (℃)NA
Half LifeApproximately 18 days
DescriptionDaratumumab is an anti-cancer drug indicated for multiple myeloma in patients who have received at least 3 prior treatments. It was granted accelerated approval by the FDA in November 2016. Marketed under the brand name Darzalex by Janssen Biotech, daratumumab is the first monoclonal antibody injection approved for this indication and provides another options for patients with multiple myeloma resistant to other therapies. Daratumumab induces apoptosis of cancer cells by targeting the CD38 epitope, which is highly expressed on haematological malignancies.
Indication/DiseaseFor the treatment of patients with multiple myeloma who have received at least three prior lines of therapy (a proteasome inhibitor (PI) and an immunomodulatory agent) or who are double-refractory to a PI and an immunomodulatory agent. This indication was approved by accelerated approval based on response rate.
PharmacodynamicsIn preclinical trials, daratumumab showed synergistic activity with other multiple myeloma therapies, notably lenalidomide. Daratumumab also causes lysis in other cells that express CD38: myeloid-derived suppressor cells, a subset of regulatory T-cells, and NK cells. Decreases in absolute count and percentage of NK cells were observed during treatment. CD4+ and CD8+ T cell absolute counts as well the percentage of total lymphocytes increased in peripheral blood and bone marrow during daratumumab treatment.
Mechanism of ActionDaratumumab is an immunoglobulin G1 kappa monoclonal antibody against CD38 antigen. CD38 is a transmembrane glycoprotein of many functions, including receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. CD38 is expressed on many cell types and tissues, and highly expressed in haematological malignancies including multiple myeloma tumor cells. By binding CD38, daratumumab causes inhibition of tumor cell growth and induces broad-spectrum apoptosis in multiple ways: by Fc-mediated cross linking, by immune-mediate tumor cell lysis through complement dependent cytotoxicity, antibody dependent cell cytotoxicity, and antibody dependent cellular phagocytosis.
ToxicityImmunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Due to its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density. The FDA label recommends to defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed. Women of reproductive potential should also should use effective contraception methods during treatment and 3 months post-treatment to avoid pregnancy and exposure to the fetus while on daratumumab.
MetabolismNA
AbsorptionFollowing the recommended schedule and dose of 16 mg/kg, the mean serum Cmax value was 915 μg/mL at the end of weekly dosing, approximately 2.9-fold higher than following the first infusion. The mean predose serum concentration at the end of weekly dosing was 573 μg/mL.
Volume of Distribution4.7 L
Clearance171.4 mL/day. Clearance decreased with increasing dose and repeated dosing, indicating target-mediated pharmacokinetics.
CategoriesAntineoplastic Agents
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1
Information of corresponding available drug in the market
Brand NameNA
CompanyNA
Brand DiscriptionNA
Prescribed forNA
Chemical NameNA
Formulation100 mg/5mL
Physcial AppearanceSolution, concentrate
Route of AdministrationIV
Recommended DosageInjection
ContraindicationNA
Side EffectsNA
Useful Linkhttp://www.rxlist.com/darzalex-drug.htm
PubMed ID28259300, 28205194, 28123899, 27195659, 26651519, 26362528, 24284914, 27363832, 27195659
3-D StructureN.A.


Entry 2
(2) Primary information
ID1724
ThPP IDTh1174
Therapeutic Peptide/Protein NameDaratumumab
SequenceNA view full sequnce in fasta
Functional ClassificationIIIc
Molecular Weight148000
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting Point (℃)NA
Half LifeApproximately 18 days
DescriptionDaratumumab is an anti-cancer drug indicated for multiple myeloma in patients who have received at least 3 prior treatments. It was granted accelerated approval by the FDA in November 2016. Marketed under the brand name Darzalex by Janssen Biotech, daratumumab is the first monoclonal antibody injection approved for this indication and provides another options for patients with multiple myeloma resistant to other therapies. Daratumumab induces apoptosis of cancer cells by targeting the CD38 epitope, which is highly expressed on haematological malignancies.
Indication/DiseaseFor the treatment of patients with multiple myeloma who have received at least three prior lines of therapy (a proteasome inhibitor (PI) and an immunomodulatory agent) or who are double-refractory to a PI and an immunomodulatory agent. This indication was approved by accelerated approval based on response rate.
PharmacodynamicsIn preclinical trials, daratumumab showed synergistic activity with other multiple myeloma therapies, notably lenalidomide. Daratumumab also causes lysis in other cells that express CD38: myeloid-derived suppressor cells, a subset of regulatory T-cells, and NK cells. Decreases in absolute count and percentage of NK cells were observed during treatment. CD4+ and CD8+ T cell absolute counts as well the percentage of total lymphocytes increased in peripheral blood and bone marrow during daratumumab treatment.
Mechanism of ActionDaratumumab is an immunoglobulin G1 kappa monoclonal antibody against CD38 antigen. CD38 is a transmembrane glycoprotein of many functions, including receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. CD38 is expressed on many cell types and tissues, and highly expressed in haematological malignancies including multiple myeloma tumor cells. By binding CD38, daratumumab causes inhibition of tumor cell growth and induces broad-spectrum apoptosis in multiple ways: by Fc-mediated cross linking, by immune-mediate tumor cell lysis through complement dependent cytotoxicity, antibody dependent cell cytotoxicity, and antibody dependent cellular phagocytosis.
ToxicityImmunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Due to its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density. The FDA label recommends to defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed. Women of reproductive potential should also should use effective contraception methods during treatment and 3 months post-treatment to avoid pregnancy and exposure to the fetus while on daratumumab.
MetabolismNA
AbsorptionFollowing the recommended schedule and dose of 16 mg/kg, the mean serum Cmax value was 915 μg/mL at the end of weekly dosing, approximately 2.9-fold higher than following the first infusion. The mean predose serum concentration at the end of weekly dosing was 573 μg/mL.
Volume of Distribution4.7 L
Clearance171.4 mL/day. Clearance decreased with increasing dose and repeated dosing, indicating target-mediated pharmacokinetics.
CategoriesAntineoplastic Agents
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1
Information of corresponding available drug in the market
Brand NameDarzalex
CompanyJanssen Biotech, Inc.
Brand DiscriptionDARZALEX is supplied as a colorless to pale yellow preservative-free solution for intravenous infusion in single-dose vials. The pH is 5.5. DARZALEX must be diluted with 0.9% Sodium Chloride Injection, USP
Prescribed forDARZALEX is indicated for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.
Chemical NameNA
Formulation100 mg/5mL
Physcial AppearanceSolution, concentrate
Route of AdministrationIV
Recommended DosageThe recommended dose of DARZALEX is 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule.
ContraindicationThe dose of DARZALEX at which severe toxicity occurs is not known.
Side EffectsInfusion reactions
Useful Linkhttp://www.rxlist.com/darzalex-drug.htm
PubMed ID28259300, 28205194, 28123899, 27195659, 26651519, 26362528, 24284914, 27363832, 27195659
3-D StructureN.A.