CPC A61K 38/195 (2013.01) [A61K 31/138 (2013.01); A61K 31/395 (2013.01); A61K 31/403 (2013.01); A61K 31/451 (2013.01); A61K 31/4545 (2013.01); A61K 31/47 (2013.01); A61K 31/495 (2013.01); A61K 31/5415 (2013.01); A61K 38/12 (2013.01); A61K 39/3955 (2013.01); A61P 35/00 (2018.01); C07K 16/286 (2013.01); C07K 16/2866 (2013.01); A61K 2039/505 (2013.01); A61K 2039/507 (2013.01); C07K 2317/21 (2013.01); C07K 2317/76 (2013.01)] | 12 Claims |
1. A method of inhibiting cancer progression in a cancer patient having a CXCR4-HRH1 (CXC receptor 4-Histamine Receptor H1) heteromer in a cancer cell, the method comprising:
administering to a cancer patient having a CXCR4-HRH1 heteromer in a cancer cell an inhibitor of CXCR4 and an inhibitor of HRH1;
wherein:
i) the CXCR4-HRH1 heteromer has enhanced downstream signaling relative to downstream signaling from a CXCR4 protomer or HRH1 protomer; and
ii) the administered inhibitor or combination of inhibitors suppresses the enhanced downstream signaling from said CXCR4-HRH1 heteromer in the cell wherein the CXCR4 inhibitor is selected from the group consisting of: AD-114, AD-114-6H, AD-114-Im7-FH, AD-114-PA600-6H, ALX-0651, ALX40-4C, AMD070 (AMD11070, X4P-001), AMD3100 (plerixafor), AMD3465, ATI 2341, BKT140 (BL-8040; TF14016; 4F-Benzoyl-TN14003), CTCE-9908, CX549, D-[Lys3] GHRP-6, FC122, FC131, GMI-1359, GSK812397, GST-NT21MP, isothiourea-1a, isothiourea-It (ITlt), KRH-1636, KRH-3955, LY2510924, LY2624587, MSX-122, N-[uC]Methyl-AMD3465, PF-06747143, POL6326, SDF-1 1-9[P2G] dimer, SDF1 P2G, T134, T140, T22, TC 14012, TG-0054 (Burixafor), USL311, ulocuplumab (MDX1338/BMS-936564), viral macrophage inflammatory protein-II (vMIP-II), WZ811, 12G5, 238D2, 238D4, [64Cu]-AMD3100, [64Cu]-AMD3465, [68Ga]pentixafor, [90Y]pentixather, [99mTc]02-AMD3100, [177Lu]pentixather, and 508MCl (Compound 26);
wherein the HRH1 inhibitor is selected from the group consisting of: (−)-chlorpheniramine, (+)-chlorpheniramine, (−)-trans-H2-PAT, (+)-cis-H2-PAT, (+)-trans-H2-PAT, (±)-cis-H2-PAT, (±)-trans-H2-PAT, (R)-cetirizine, (S)-cetirizine, 9-OH-risperidone, A-317920, A-349821, ABT-239, alimemazine, amitriptyline, aripiprazole, arpromidine, asenapine, astemizole, AZD3778, azelastine, BU-E 47, cetirizine, chlorpheniramine, chlorpromazine, ciproxifan, clemastine, clobenpropit, clozapine, conessine, cyclizine, cyproheptadine, desloratadine, diphenhydramine, dosulepin, doxepin, epinastine, fexofenadine, fluphenazine, fluspirilene, haloperidol, hydroxyzine, impromidine, INCB-38579, JNJ-39758979, ketotifen, loratadine, loxapine, MK-0249, molindone, olanzapine, perphenazine, pimozide, pipamperone, pitolisant, promethazine, pyrilamine, quetiapine, risperidone, sertindole, terfenadine, thioridazine, thiothixene, trifluoperazine, tripelennamine, triprolidine, ziprasidone, and zotepine; and
wherein the cancer is a solid tumor.
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