Elotuzumab - Drugbank

Home , Elotuzumab

11/8/2018 Elotuzumab - DrugBank

Elotuzumab

Targets (1) Biointeractions (1)

IDENTIFICATION

Name Elotuzumab

Accession Number DB06317

Type

Biotech

Groups

Approved

Biologic Classiﬁcation Protein Based Therapies Monoclonal antibody (mAb)

Description Elotuzumab is a humanized IgG1 (Immunoglobulin G) monoclonal antibody indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies. Elotuzumab targets SLAMF7, also known as Signaling Lymphocytic Activation Molecule Family member 7, a cell surface glycoprotein. Elotuzumab consists of the complementary determining regions (CDR) of the mouse antibody, MuLuc63, graed onto human IgG1 heavy and kappa light chain frameworks. Elotuzumab is produced in NS0 cells by recombinant DNA technology. Elotuzumab has a theoretical mass of 148.1 kDa for the intact antibody. Elotuzumab was approved on November 30, 2015 by the U.S. Food and Drug Administration. Elotuzumab is marketed under the brand Empliciti™ by Bristol-Myers Squibb.

https://wwwP t.drugbank.ca/drugs/DB06317i t t 1/12 11/8/2018 Elotuzumab - DrugBank Protein structure

Protein chemical formula

C6476H9982N1714O2016S42

Protein average weight 148100.0 Da

Sequences

>Elotuzumab heavy chain EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINY APSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK

>Elotuzumab light chain DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPD RFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Download FASTA Format

Synonyms

HuLuc63

Immunoglobulin G1, anti-(human protein CS1) (human-mouse HuLuc63 heavy chain), disulﬁde with human-mous e HuLuc63 kappa-chain, dimer

Immunoglobulin G1, anti-(human SLAM family member 7 (CD2-like receptor activating cytotoxic cells, CD319 ant igen)), humanized mouse monoclonal HuLuc63 gamma-1 heavy chain (222-214')-disulﬁde with humanized mouse monoclonal HuLuc63 kappa light chain (228-228'';231-231'')-bisdisulﬁde dimer

External IDs

BMS 901608 / PDL 063 / PDL063 / UNII 1351PE5UGS https://www.drugbank.ca/drugs/DB06317 2/12 11/8/2018 Elotuzumab - DrugBank BMS-901608 / PDL 063 / PDL063 / UNII-1351PE5UGS

Prescription Products

MARKETING MARKETING NAME ↑↓ DOSAGE ↑↓ STRENGTH ↑↓ ROUTE ↑↓ LABELLER ↑↓ START ↑↓ END ↑↓ ↑↓ ↑↓

Empliciti Powder, for 340 mg Intravenous Bristol Myers Not applicable Not applicable solution Squibb

Empliciti Injection, 300 mg Intravenous Bristol Myers 2016-05-11 Not applicable powder, for Squibb solution

Empliciti Injection, 400 mg/1 Intravenous E.R. Squibb & 2015-11-30 Not applicable powder, Sons, L.L.C. lyophilized, for solution

Empliciti Powder, for 440 mg Intravenous Bristol Myers Not applicable Not applicable solution Squibb

Empliciti Injection, 300 mg/1 Intravenous E.R. Squibb & 2015-11-30 Not applicable powder, Sons, L.L.C. lyophilized, for solution

Empliciti Injection, 400 mg Intravenous Bristol Myers 2016-05-11 Not applicable powder, for Squibb solution

Showing 1 to 6 of 6 entries ‹ ›

Categories

Amino Acids, Peptides, and Proteins

Antibodies

Antibodies, Monoclonal

Antineoplastic Agents

Blood Proteins

Globulins

Immunoglobulins

Immunoproteins https://www.drugbank.ca/drugs/DB06317 3/12 11/8/2018 p Elotuzumab - DrugBank

Proteins

Serum Globulins

SLAMF7-directed Antibody Interactions

SLAMF7-directed Immunostimulatory Antibody

UNII 1351PE5UGS

CAS number 915296-00-3

PHARMACOLOGY

Indication

Indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

Associated Conditions

Refractory Multiple Myeloma

Pharmacodynamics

Not Available

Mechanism of action

Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on Natural Killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage. Elotuzumab directly activates Natural Killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with Natural Killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC). In preclinical models, the combination of elotuzumab and lenalidomide resulted in enhanced activation of Natural Killer cells that was greater than the effects of either agent alone and increased anti-tumor activity in vitro and in vivo.

https://www.drugbank.ca/drugs/DB06317 4/12 11/8/2018 Elotuzumab - DrugBank

A SLAM family member 7

modulator

Human

Absorption Not Available

Volume of distribution Not Available

Protein binding Not Available

Metabolism

Not Available

Route of elimination Not Available

Half life

Not Available

Clearance

The clearance of elotuzumab decreased from a geometric mean (CV%) of 17.5 (21.2%) to 5.8 (31%) mL/day/kg with an increase in dose from 0.5 (i.e., 0.05 times the recommended dosage) to 20 mg/kg (i.e., 2 times the recommended dosage). Based on a population PK model, when elotuzumab is given in combination with lenalidomide and dexamethasone, approximately 97% of the maximum steady-state concentration is predicted to be eliminated with a geometric mean (CV%) of 82.4 (48%) days.

Toxicity

Not Available

Aﬀected organisms

Humans and other mammals

Pathways

Not Available https://www.drugbank.ca/drugs/DB06317 5/12 11/8/2018 Elotuzumab - DrugBank

Pharmacogenomic Eﬀects/ADRs

Not Available

INTERACTIONS

Drug Interactions

ALL DRUGS APPROVED VET APPROVED NUTRACEUTICAL ILLICIT WITHDRAWN

INVESTIGATIONAL EXPERIMENTAL

DRUG ↑↓ INTERACTION ↑↓ Abciximab The risk or severity of adverse eﬀects can be increased when Abciximab is combined with Elotuzumab.

Abituzumab The risk or severity of adverse eﬀects can be increased when Elotuzumab is combined with Abituzumab.

Adalimumab The risk or severity of adverse eﬀects can be increased when Adalimumab is combined with Elotuzumab.

Adecatumumab The risk or severity of adverse eﬀects can be increased when Adecatumumab is combined with Elotuzumab.

Aducanumab The risk or severity of adverse eﬀects can be increased when Elotuzumab is combined with Aducanumab.

Afelimomab The risk or severity of adverse eﬀects can be increased when Afelimomab is combined with Elotuzumab.

Alemtuzumab The risk or severity of adverse eﬀects can be increased when Alemtuzumab is combined with Elotuzumab.

Alirocumab The risk or severity of adverse eﬀects can be increased when Elotuzumab is combined with Alirocumab.

Amatuximab The risk or severity of adverse eﬀects can be increased when Elotuzumab is combined with Amatuximab.

AMG 108 The risk or severity of adverse eﬀects can be increased when AMG 108 is combined with Elotuzumab.

Showing 1 to 10 of 238 entries ‹ ›

Food Interactions https://www.drugbank.ca/drugs/DB06317 6/12 11/8/2018 Elotuzumab - DrugBank

Not Available

REFERENCES

Synthesis Reference

"Patent Link":https://www.google.com/patents/WO2014055370A1?cl=en

General References

1. Hsi ED, Steinle R, Balasa B, Szmania S, Draksharapu A, Shum BP, Huseni M, Powers D, Nanisetti A, Zhang Y, Rice AG, van Abbema A, Wong M, Liu G, Zhan F, Dillon M, Chen S, Rhodes S, Fuh F, Tsurushita N, Kumar S, Vexler V, Shaughnessy JD Jr, Barlogie B, van Rhee F, Hussein M, Afar DE, Williams MB: CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008 May 1;14(9):2775- 84. doi: 10.1158/1078-0432.CCR-07-4246. [PubMed:18451245] 2. Tai YT, Dillon M, Song W, Leiba M, Li XF, Burger P, Lee AI, Podar K, Hideshima T, Rice AG, van Abbema A, Jesaitis L, Caras I, Law D, Weller E, Xie W, Richardson P, Munshi NC, Mathiot C, Avet-Loiseau H, Afar DE, Anderson KC: Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood. 2008 Aug 15;112(4):1329-37. Epub 2007 Sep 28. [PubMed:17906076] 3. Markham A: Elotuzumab: First Global Approval. Drugs. 2016 Mar;76(3):397-403. doi: 10.1007/s40265-016-0540-0. [PubMed:26809244]

External Links KEGG Drug

D09337

PubChem Substance

347910347

ChEMBL CHEMBL1743010

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

PDRhealth PDRhealth Drug Page

Wikipedia Elotuzumab https://www.drugbank.ca/drugs/DB06317 7/12 11/8/2018 Elotuzumab - DrugBank

AHFS Codes

10:00.00 — Antineoplastic Agents

FDA label

Download (245 KB)

MSDS

Download (381 KB)

CLINICAL TRIALS

Clinical Trials

PHASE ↑↓ STATUS ↑↓ PURPOSE ↑↓ CONDITIONS ↑↓ COUNT ↑↓ 1 Completed Treatment Multiple Myeloma (MM) 5

1 Terminated Treatment Multiple Myeloma (MM) 2

1, 2 Active Not Treatment DS Stage I Plasma Cell Myeloma / DS Stage II Plasma 1 Recruiting Cell Myeloma / DS Stage III Plasma Cell Myeloma / Multiple Myeloma (MM) / Plasma Cell Myeloma

1, 2 Recruiting Treatment Plasma Cell Myeloma 1

2 Active Not Treatment Multiple Myeloma (MM) 4 Recruiting

2 Active Not Treatment Relapsed and/or Refractory Multiple Myeloma 1 Recruiting

2 Active Not Treatment Smoldering Multiple Myeloma (SMM) / Smoldering 1 Recruiting Myeloma

2 Completed Treatment Hematologic Cancers 1

2 Completed Treatment Multiple Myeloma (MM) 2

2 Completed Treatment Smoldering Multiple Myeloma (SMM) 1

Showing 1 to 10 of 23 entries ‹ ›

PHARMACOECONOMICS

Manufacturers https://www.drugbank.ca/drugs/DB06317 8/12 11/8/2018 Elotuzumab - DrugBank

Not Available

Packagers

Not Available

Dosage forms

FORM ↑↓ ROUTE ↑↓ STRENGTH ↑↓ Injection, powder, for solution Intravenous 300 mg

Injection, powder, for solution Intravenous 400 mg

Injection, powder, lyophilized, for solution Intravenous 300 mg/1

Injection, powder, lyophilized, for solution Intravenous 400 mg/1

Powder, for solution Intravenous 340 mg

Powder, for solution Intravenous 440 mg

Showing 1 to 6 of 6 entries ‹ ›

Prices

Not Available

Patents

PATENT NUMBER ↑↓ PEDIATRIC EXTENSION ↑↓ APPROVED ↑↓ EXPIRES (ESTIMATED) ↑↓ ↑↓

US2014055370 No 2012-10-01 2032-10-01

Showing 1 to 1 of 1 entries ‹ ›

PROPERTIES

State

Solid

Experimental Properties https://www.drugbank.ca/drugs/DB06317 9/12 11/8/2018 Elotuzumab - DrugBank Not Available

TAXONOMY

Description Not Available

Kingdom Organic Compounds

Super Class Organic Acids

Class Carboxylic Acids and Derivatives

Sub Class

Amino Acids, Peptides, and Analogues

Direct Parent

Peptides

Alternative Parents

Not Available

Substituents

Not Available

Molecular Framework Not Available

External Descriptors Not Available

TARGETS

https://www.drugbank.ca/drugs/DB06317 10/12 11/8/2018 Elotuzumab - DrugBank 1. SLAM family member 7

Kind

Protein

Organism Human

Pharmacological action

Yes

Actions

Modulator General Function

Not Available

Speciﬁc Function

Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and diﬀer...

Gene Name

SLAMF7

Uniprot ID Q9NQ25

Uniprot Name SLAM family member 7

Molecular Weight

37420.62 Da

References

1. Markham A: Elotuzumab: First Global Approval. Drugs. 2016 Mar;76(3):397-403. doi: 10.1007/s40265- 016-0540-0. [PubMed:26809244]

Drug created on March 19, 2008 10:24 / Updated on November 08, 2018 04:37

https://www.drugbank.ca/drugs/DB06317 11/12 11/8/2018 Elotuzumab - DrugBank About

About DrugBank DrugBank Blog Wishart Research Group

Support FAQ Help Email Support

Commercial Products API Pricing API Docs Data Licenses

Support

This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-proﬁt organization that is leading Canada's national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc.

https://www.drugbank.ca/drugs/DB06317 12/12