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Ion Channels as Therapeutic Antibody Targets

Increase Your Efficiency and Value Antibodies, antigens, etc. for your research and discovery Introduction

Ion channels act by transporting ions across cell membranes and play an important role in a wide range of physiological and pathophysiological processes. To date, the focus of most drug developments has been the identification and development of small molecule and peptide modulators, primarily due to the lack of structural and functional information. Many ion channel modulators have been discovered from studies of naturally occurring materials. Recently, alternative approaches for targeting ion channels have included monoclonal antibodies (mAbs), but their therapeutic potential has been largely underdeveloped.

Advantages of targeting ion channels with antibodies

◆ Selectivity

• With respect to ion channels, this has been particularly challenging as ion channels within a given family often share high levels of homology, notably within the pore- forming domains where many channel blockers exert their effect, but have vastly different physiological roles. An obvious alternative to small molecule promiscuity is the development of mAbs, where high levels of specificity would be expected to mitigate off-target effects, and therefore generate safer classes of drugs.

◆ Biodistribution, half-life and effector functions

• Limiting (CNS) penetration (when targeting a therapeutic to the periphery); • Low variability in patient pharmacokinetics; • Longer duration of action leading to reduced dosing.

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Ion Channel Therapeutic Area/Indication

MS, RA, T1D, Atopic dermatitis, Uveitis, DED, Psoriasis myositis, Cutaneous lupus, Kv1.3 Psoriatic arthritis, IBD, Allergic asthma, Atopic dermatitis, Psoriasis

Kv10.2 Brain cancer, Lung cancer, Cervical cancer

Kv11.1 Some cancers (Leukemias, Gastric, Colon)

Autoimmune, IBD, MS, RA, Asthma, Fibrosis, Sickle cell anemia, Breast, Prostate, KCa3.1 Pancreatic, Endometrial, GBM, HNSCC, Leukemia, ICC, Melanoma

Cav3.1 Breast cancer, Prostate cancer

Nav1.7 Pain

ASIC1 Pain

TRPA1 Pain, Inflammation

TRPC3 AP, SS, Hypertension, Atherosclerosis, COPD

TRPV3 Skin health, Inflammation, Pain

P2X2; P2X3 Pain, Fibrosis, Chronic cough

P2X4 Pain

P2X7 Basal cell carcinoma

CRAC Autoimmune disease, Inflammatory disease, Psoriasis, AP

Abbreviations and acronyms used in table:

AP: Acute pancreatitis IBD: Inflammatory bowel disorder COPD: Chronic obstructive pulmonary disease MS: Multiple sclerosis DED: Dry eye disease RA: Rheumatoid arthritis GBM: Glioblastoma SS: Sjögren’s syndrome HNSCC: Head and neck squamous cell carcinoma T1D: Type 1 diabetes

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The targets involving ion channels

Ion Channels Targets

Voltage-gated potassium ion channels Kv1.3; Kv10.1; Kv2.1; Kv11.1

Calcium-activated potassium ion channels Kca3.1

Voltage-gated calcium ion channels Cav3.1; Cav3.2

Voltage-gated sodium ion channels Nav1.7; Nav1.8; Nav1.9; Nav1.5; nNav1.5

ASIC channels ASIC1a

TRPM7; TRPM8; TRPV1; TRPV3; TRPV6; TRPA1; TRP channels TRPC3; TRPC6

Ligand-gated purinergic P2X channels P2X3; P2X4; P2X7

Calcium-release activated channels CRAC

Chloride channels CLCs; CACCs

Reference:

Catherine J. Hutchings, Paul Colussi, Theodore G. Clarka. (2019). Ion channels as therapeutic antibody targets. Taylor & Francis Group, 11(2), 265-296.

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Featured antibodies related to ion channel

Targets Clone Applications Species Reactivity Cat.

KCNA3 L23-27 IS, WB, IHC Mammal CBMAB-K0477-LY

KCNA3 CBLY1-045 WB, IP, IF, ELISA Mouse, Rat, Human CBMAB-K0475-LY

KCNA3 S23-27 IHC, IF, EM, WB Rat CBMAB-K0478-LY

KCNA3 1D8 WB Human CBMAB-K0476-LY

KCNH1 C11 WB, IP, IF, ELISA Mouse, Rat, Human CBMAB-K0535-LY

KCNH1 CBLY1-048 WB Human CBMAB-K0534-LY

KCNB1 L80-21 IS, WB, IHC Mammal CBMAB-K0505-LY

KCNB1 K89-34 WB, IHC-P Mouse, Rat, Human CBMAB-K0504-LY

KCNB1 S89-34 IHC, IF, EM, IP, WB Human, Mouse, Rat CBMAB-K0508-LY

KCNH2 CBFYH-2603 WB, IP, IF, ELISA Mouse, Rat, Human CBMAB-H3629-FY

KCNH2 D1Y2J WB, IP Human, Rat, Monkey CBMAB-H3628-FY

CACNA1G N178A-9 Immunostaining, WB, IHC Mammal CBMAB-C9610-LY

CACNA1G S178A-9 WB, IHC Human, Mouse, Rat CBMAB-C2259-CQ

CACNA1H N55-10 Immunostaining, IHC Human CBMAB-C9612-LY

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Targets Clone Applications Species Reactivity Cat.

CACNA1H 10F690 IF, IHC, IP, WB Human, Mouse CBMAB-C1231-CN

CACNA1H S55-10 IF, IHC-Fr, IP, WB Human, Mouse, Rat CBMAB-1262-CN

SCN9A D5L1J WB, IP Human, Mouse, Rat CBMAB-CP2371-LY

SCN9A N68/6 IHC, WB Human CBMAB-S6449-CQ

SCN9A CBXS-5134 ELISA, WB Human CBMAB-S2352-CQ

SCN10A CBXS-0152 ICC, IHC-P, WB Rat CBMAB-S3141-CQ

SCN10A CBXS-5368 WB, IP Human, Mouse, Rat CBMAB-S2581-CQ

Human, Monkey, SCN10A CBWJN-0038 ICC, IF, IHC, WB CBMAB-N4242-WJ Mouse, Rat

SCN10A S134-12 WB, IHC-P, ICC Human, Mouse, Rat CBMAB-N0595-WJ

SCN11A 2B10 WB, ELISA Human CBMAB-A7928-LY

SCN11A 6E1 WB, ELISA Human CBMAB-A7927-LY

SCN11A CBXS-3370 ELISA, WB Human CBMAB-S6107-CQ

SCN11A CBXS-2831 ELISA, WB Human CBMAB-S5581-CQ

SCN5A D9J7S WB, IP Human, Mouse, Rat CBMAB-CP2370-LY

SCN5A 4G8: 1G7 FC, IHC, IF, WB Human CBMAB-XB1028-YC

WB, FC, ELISA, IHC, SCN5A ERIC-1 Human CBMAB-N0599-WJ IF, IP, RIA, CyTOF

ASIC1 N271-44 WB, IHC Mouse, Rat CBMAB-1147-CN

TRPM7 CBYJT-4919 ICC, IHC-P, IP, WB Mouse, Human, Rat CBMAB-T4473-YJ

TRPM7 CBYJT-4918 WB, ELISA Human, Rat, Mouse CBMAB-T4471-YJ

TRPM7 CBYJT-4917 WB, ICC, IF Human, Mouse, Rat CBMAB-T4470-YJ

TRPM8 CBYJT-4922 WB, ELISA, ICC Human, Rat, Mouse CBMAB-T4476-YJ

TRPM8 CBYJT-4920 ICC, WB Human, Mouse CBMAB-T4474-YJ

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Targets Clone Applications Species Reactivity Cat.

TRPV1 1F5 IF, IHC, IP, WB Human, Rat CBMAB-A9552-LY

TRPV1 CBYJT-4924 ELISA, WB Human CBMAB-T4478-YJ

TRPV1 BS397 WB, IHC-Fr Mouse, Rat CBMAB-V0032-YC

TRPV3 CBYJT-4926 ICC, IHC-P, IP, WB Rat, Mouse, Human CBMAB-T4482-YJ

TRPV3 S15-4 WB, IHC, ICC, IF, IP, AM Rat, Mouse, Human CBMAB-T4481-YJ

TRPV3 S15-39 WB, IF, ICC, IP Rat, Mouse, Human CBMAB-T4480-YJ

TRPV3 CBYY-1232 WB, IHC, IP Rat CBMAB-1236-YY

TRPA1 CBYJT-4895 ELISA, WB Human CBMAB-T4441-YJ

TRPC3 D4P5S WB, IP Human, Mouse, Rat CBMAB-CP2878-LY

TRPC3 CBYJT-4899 WB, IP, IF, ELISA Human, Rat, Mouse CBMAB-T4445-YJ

TRPC6 CBYJT-4909 IP, WB Human, Mouse, Rat CBMAB-T4458-YJ

TRPC6 CBYJT-4910 EIA, IHC-P, WB Human, Chimpanzee CBMAB-T4459-YJ

TRPC6 CBYJT-4908 ELISA, IHC, WB Human CBMAB-T4456-YJ

P2RX4 CBYC-P121 WB Human CBMAB-P0584-YC

P2RX7 E1E8T WB, IP Human CBMAB-CP1826-LY

P2RX7 REA875 FC Mouse CBMAB-P0591-YC

P2RX7 Hano43 FC, ICC, IF Mouse CBMAB-P0590-YC

P2RX7 1F11 FC Mouse CBMAB-P0588-YC

Human, Mouse, Rat, ORAI1 D90B10 WB CBMAB-CP3189-LY Monkey

ORAI1 CBXO-0232 ELISA, IF, IHC, WB Human, Mouse, Rat CBMAB-O0511-CQ

ORAI1 CBXO-0408 ELISA, WB, IHC Human CBMAB-O0510-CQ

ABCB1 CBXC-0864 FC Human CBMAB-C1979-CQ

ABCB1 CBFYM-0442 IHC-P, IHC-Fr, IP, FC Human CBMAB-M0558-FY

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Since 2004, Creative Biolabs has been working on the development of tumor markers and the production of antibodies against of ion channels.

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