Most of molecules enter or leave cells mainly via membrane transport proteins, which play important roles in several cellular functions, including cell metabolism, ion homeostasis, signal transduction, binding with small molecules in extracellular space, the recognition process in the immune system, energy transduction, osmoregulation, and physiological and developmental processes. There are three major types of transport proteins, ATP-powered pumps, channel proteins and transporters.

ATP-powered pumps are ATPases that use the energy of ATP hydrolysis to move ions or small molecules across a membrane against a chemical concentration gradient or electric potential. Channel proteins transport water or specific types of ions down their concentration or electric potential gradients. Many other types of channel proteins are usually closed, and open only in response to specific signals. Because these types of ion channels play a fundamental role in the functioning of nerve cells. Transporters, a third class of membrane transport proteins, move a wide variety of ions and molecules across cell membranes. Membrane transporters either enhance or restrict drug distribution to the target organs. Depending on their main function, these membrane transporters are divided into two categories: the efflux (export) and the influx (uptake) transporters.

Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. In the central nervous system ion channels have been linked to many diseases such, but not limited to, ataxias, paralyses, epilepsies, and deafness indicative of the roles of ion channels in the initiation and coordination of movement, sensory perception, and encoding and processing of information. Furthermore, drug transporters can serve as drug targets or as a mechanism to facilitate drug delivery to cells and tissues.

References:
[1] Sadée W, et al. Pharm Res. 1995 Dec;12(12):1823-37.
[2] Girardin F. Dialogues Clin Neurosci. 2006;8(3):311-21.
[3] Zaydman MA, et al. Chem Rev. 2012 Dec 12;112(12):6319-33.
[4] Mishra NK, et al. PLoS One. 2014 Jun 26;9(6):e100278.


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NS 19504

NS19504 is a Ca2+-activated K+ channel (BK channel, KCa1.1 channel) activator (EC50=11.0 µM) with relaxing effect on bladder smooth muscle spontaneous phasic contractions[1].

  • CAS Number: 327062-46-4
  • MF: C10H9BrN2S
  • MW: 269.16100
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NS3861

NS3861 is an agonist of nicotinic acetylcholine receptors (nAChRs) and binds with high affinity to heteromeric α3β4 nAChR. The binding Ki values of 0.62, 25, 7.8, 55 nM for α3β4, α3β2, α4β4, α4β2, respectively[1].

  • CAS Number: 216853-59-7
  • MF: C12H14BrNS
  • MW: 284.22
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VU591

VU591 is a potent, selective renal outer medullary potassium channel (ROMK or Kir1.1) inhibitor, with an IC50 of 0.24 μM[1].

  • CAS Number: 1222810-74-3
  • MF: C16H12N6O5
  • MW: 368.30
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Irampanel

Irampanel (BIIR 561) is an AMPA receptor and voltage-dependent sodium channel blocker. Irampanel inhibits kainate-induced currents in rat cortical neurons[1].

  • CAS Number: 206260-33-5
  • MF: C18H19N3O2
  • MW: 309.36200
  • Catalog: iGluR
  • Density: 1.145g/cm3
  • Boiling Point: 471.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 238.9ºC

PEPA

PEPA is an allosteric modulator of AMPA receptors; binds to the GluA2o and GluA3o LBDs and can be utilized as an indicator of AMPA receptor heterogeneity.IC50 value:Target: AMPAR modulatorin vitro: PEPA dose-dependently potentiated AMPA-induced increase of [Ca2+]i. In 90% (72 out of 80) of the cells in which cyclothiazide acts, PEPA potentiated the increased [Ca2+]i induced by AMPA with pronounced cell-to-cell variation in rat hippocampal cultures [1]. PEPA bound to the binding domains of the GluA2 and GluA3 flop isoforms of AMPA receptors [2]. coapplication of AMPA with PEPA protected hippocampal CA1 neurons from brain ischemia-induced death. Coapplication of AMPA with PEPA could prevent downregulated expression of GluR2 subunit caused by ischemia and increase BDNF expression via Lyn-ERK1/2-CREB signaling [4].in vivo: PEPA (3, 10, 30mg/kg body weight) or vehicle was intraperitoneally administered into stressed mice once before the first extinction session. The significant decrease of the freezing response in the extinction sessions was only seen in the 30mg/kg PEPA-administered stressed mice, compared with vehicle-administered stressed mice [3].

  • CAS Number: 141286-78-4
  • MF: C16H16F2N2O4S2
  • MW: 402.43600
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRS 1845

MRS1845 is a Ca2+ channel blocker with relative specificity for store-operated calcium entry (SOCE) channels[1].

  • CAS Number: 544478-19-5
  • MF: C21H22N2O6
  • MW: 398.41
  • Catalog: Calcium Channel
  • Density: 1.318g/cm3
  • Boiling Point: 530.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.8ºC

Astressin 2B

Astressin 2B is a potent and selective corticotropin-releasing factor receptor 2 (CRF2) antagonist, with the IC50 values of 1.3 nM and > 500 nM for CRF2 and CRF1, respectively. Astressin 2B antagonizes CRF2-mediated inhibition of gastric emptying[1][2][3].

  • CAS Number: 681260-70-8
  • MF: C183H307N49O53
  • MW: 4041.69000
  • Catalog: CFTR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ru-32514

Ru-32514 is an agonist of benzodiazepine receptor.

  • CAS Number: 90807-98-0
  • MF: C18H17N3O2
  • MW: 307.346
  • Catalog: GABA Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GDC-0310

GDC-0310 is a selective acyl-sulfonamide Nav1.7 inhibitor, with an IC50 of 0.6 nM for hNav1.7[1].

  • CAS Number: 1788063-52-4
  • MF: C25H28Cl2FNO3
  • MW: 480.3991232
  • Catalog: Sodium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Brevetoxin2(PbTx-2)

Brevetoxin B (Brevetoxin-2; PbTx-2) is a polyketide neurotoxin produced by Karenia species and other dinoflagellates. Brevetoxin B binds to site 5 on the alpha subunit of voltage-gated sodium channels (IC50=15 nM) on neurons at the neuromuscular junction, causing the channel to open irreversibly at potentials more negative than normal, discharging action potentials repetitively. Brevetoxin B is ichthyotoxic at nanomolar concentrations and is responsible for an illness described as neurotoxic shellfish poisoning.

  • CAS Number: 79580-28-2
  • MF: C50H70O14
  • MW: 895.08200
  • Catalog: Sodium Channel
  • Density: 1.188g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PNU 282987

PNU-282987 (free base) (Compound C7) is a potent α7 nicotinic acetylcholine receptor (nAChR) agonist with an EC50 of 154 nM. PNU-282987 (free base) is also a functional antagonist of the 5-HT3 receptor with an IC50 of 4541 nM[1].

  • CAS Number: 711085-63-1
  • MF: C14H17ClN2O
  • MW: 264.75
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MCI826

MCI826 is a P-glycoprotein (P-gp) antagonist.

  • CAS Number: 140646-80-6
  • MF: C22H28N2O3S
  • MW: 400.534
  • Catalog: P-glycoprotein
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Adipiplon

Adipiplon (NG2-73) is a selective GABAA receptor positive allosteric modulator. Adipiplon is particularly useful in the treatment of a variety of central nervous system (CNS) disorders.

  • CAS Number: 840486-93-3
  • MF: C18H18FN7
  • MW: 351.38100
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tianagliflozin

Tianagliflozin is a sodium/glucose cotransporter 2 (SGLT-2) inhibitor with potential for investigation in type 2 diabetes[1].

  • CAS Number: 1461750-27-5
  • MF: C21H25ClO5
  • MW: 392.87
  • Catalog: SGLT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UBP618

UBP618 is a GluN1/GluN2 receptors pan-inhibitor.

  • CAS Number: 1333110-86-3
  • MF: C17H11BrO3
  • MW: 343.17
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YM758

YM758 is a “funny” If current channel (If channel) inhibitor.

  • CAS Number: 312752-85-5
  • MF: C26H32FN3O4
  • MW: 469.548
  • Catalog: Potassium Channel
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 680.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.3±31.5 °C

4,4'-((2beta,3alpha,5alpha,16beta,17beta)-3,17-Bis(acetyloxy)androstane-2,16-diyl)bis(1,1-dimethyl-piperazinium) dibromide

Pipecuronium bromide is a potent long-acting nondepolarizing steroidal neuromuscular blocking agent (NMBA), and a bisquaternary ammonium compound. Pipecuronium bromide is a powerful competitive nAChR antagonist with a Kd of 3.06 μM[1][2][3][4][5].

  • CAS Number: 52212-02-9
  • MF: C35H62Br2N4O4
  • MW: 762.69900
  • Catalog: nAChR
  • Density: 1.329
  • Boiling Point: N/A
  • Melting Point: 262-264ºC
  • Flash Point: N/A

Caroverine HCl

Caroverine hydrochloride is a potent, competitive and reversible antagonist of NMDA and AMPA glutamate receptor. Caroverine hydrochloride is also an antioxidant and calcium-blocking agent that exhibits vasorelaxant action. Caroverine hydrochloride can be used for the research of inner ear tinnitus[1][2][3].

  • CAS Number: 55750-05-5
  • MF: C22H28ClN3O2
  • MW: 401.93000
  • Catalog: iGluR
  • Density: 1.11g/cm3
  • Boiling Point: 521.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 269ºC

SAK 3

SAK3 (T-VGCC enhancer SAK3) is a potent, orally acitve enhancer of T-type voltage-gated Ca2+ channel (T-VGCC), enhances CaV3.1 and CaV3.3, but not CaV3.2 activity at concentrations of 0.01-10 nM in neuro2A cells in vitro; significantly enhanced acetylcholine (ACh) release in the hippocampal CA1 region of naïve mice (0.5 mg/kg, p.o.); significantly enhanced hippocampal ACh levels in olfactory-bulbectomized (OBX) mice, rescuing impaired memory-related behaviors.

  • CAS Number: 1256269-87-0
  • MF: C20H23N3O4
  • MW: 369.414
  • Catalog: Calcium Channel
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 539.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 280.0±32.9 °C

ICA-027243

ICA-27243 is a selective, potent and orally active KCNQ2/Q3 potassium channel opener with an EC50 of 0.38 μM. ICA-27243 is less effective at activating KCNQ4 and KCNQ3/Q5. ICA-27243 has antiepileptic and anticonvulsant effects[1][2].

  • CAS Number: 325457-89-4
  • MF: C12H7ClF2N2O
  • MW: 268.64700
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Flufiprole

Flufiprole is a nonsystemic phenylpyrazole insecticide targeting the GABA receptor used in the rice field. Flufiprole is excellent in controlling a wide range of pests[1].

  • CAS Number: 704886-18-0
  • MF: C16H10Cl2F6N4OS
  • MW: 491.23800
  • Catalog: GABA Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydroxy-alpha-sanshool

Hydroxy-​α-​sanshool is an alkylamide isolated from pepper, acts as a TRPA1 covalent and TRPV1 non-covalent agonist, with EC50s of 69 and 1.1 µM, respectively[1].

  • CAS Number: 83883-10-7
  • MF: C16H25NO2
  • MW: 263.37500
  • Catalog: TRP Channel
  • Density: 0.973 g/cm3
  • Boiling Point: 471.5±45.0℃ at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

Bliretrigine

Bliretrigine is a sodium channel blocker. Bliretrigine has the effect of relieving pain[1][2][3].

  • CAS Number: 1233229-75-8
  • MF: C20H24N4O2
  • MW: 352.43
  • Catalog: Sodium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tulrampator

Tulrampator (CX-1632) is an orally bioavailable positive allosteric modulator of AMPA receptor (AMPAR)[1]. Antidepressant[1].

  • CAS Number: 1038984-31-4
  • MF: C20H17FN4O3
  • MW: 380.37
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ro 0437626

Ro 0437626 is a selective purinergic (P2X1) receptor antagonist (IC50 = 3 μM), but shows low affinity for P2X2, P2X3 and P2X2/3 receptors (IC50 > 100 μM)[1].

  • CAS Number: 134362-79-1
  • MF: C27H35N5O4S
  • MW: 525.66300
  • Catalog: P2X Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alisol F

Alisol F is a natural product.

  • CAS Number: 155521-45-2
  • MF: C30H48O5
  • MW: 488.699
  • Catalog: P-glycoprotein
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 617.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.6±25.0 °C

ML 418

ML418 is the first potent, selective and CNS penetrating blocker of Kir7.1 potassium channel (IC50, 310 nM), which also potently inhibits Kir6.2/SUR1, and exhibits superior selectivity over other Kir channels[1].

  • CAS Number: 1928763-08-9
  • MF: C19H24ClN3O3
  • MW: 377.87
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mepivacaine

Mepivacaine is an amide-type local anesthetic agent. Mepivacaine binds to specific voltage-gated sodium ion channels in neuronal cell membranes, which inhibits both sodium influx and membrane depolarization[1][2].

  • CAS Number: 96-88-8
  • MF: C15H22N2O
  • MW: 246.34800
  • Catalog: Sodium Channel
  • Density: 1.077 g/cm3
  • Boiling Point: 383.062ºC at 760 mmHg
  • Melting Point: 150.5ºC
  • Flash Point: 185.47ºC

YHO-13177

YHO-13177 is a potent and specific inhibitor of BCRP; potentiated the cytotoxicity of SN-38 in cancer cells and no effect on P-glycoprotein–mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells.IC50 value:Target: BCRP inhibitorin vitro: YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38–resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein–mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1–mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells [1].in vivo: In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRP-transduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models [1].

  • CAS Number: 912287-56-0
  • MF: C20H22N2O3S
  • MW: 370.46500
  • Catalog: BCRP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGP 35348

CGP 35348 is a selective, brain penetrant, centrally active GABAB receptor antagonist with an EC50 of 34 μM. CGP 35348 shows affinity for the GABAB receptor only[1]. CGP 35348 has a potential to improve neuromuscular coordination and spatial learning in albino mouse following neonatal brain damage[2].

  • CAS Number: 123690-79-9
  • MF: C8H20NO4P
  • MW: 225.22
  • Catalog: GABA Receptor
  • Density: 1.131g/cm3
  • Boiling Point: 400.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 196ºC