Table 2.

Chemokine inhibitors for pancreatitis and pancreatic cancer.

Chemokine Inhibition for Pancreatitis Therapy
S.NO	Chemokine	Chemokine Inhibitor	Study Organism	Experimental Study	Biological Effects	References
1.	CXCR2	Antileukinate (52.63 mg/kg, s.c.)	Swiss mice	Caerulein (50 μg/kg/h) induced acute pancreatitis mediated pancreatic and lung injury	Reduced plasma amylase, pancreatic water content, pancreatic myeloperoxidase activity, pancreatic MIP-2 levels pancreas, and lung myeloperoxidase activity	[86]
2.	CCL2/MCP-1	Pepducin	BALB/c mice	Acute and chronic pancreatitis induced by intraperitoneal administration of (0.2 mg/kg body weight) caerulein	The decrease in pancreatitis induced neutrophils, macrophages, and acinar cell damage	[87]
		Bindarit; inhibitor of MCP-1,	A rat model of severe acute pancreatitis (SAP)	SAP model was induced by retrograde infusion of (4%) sodium taurocholate into the biliopancreatic duct	Bindarit ameliorates SAP by inhibiting serum amylase MCP-1, levels, and pancreatic damage	[88]
Chemokine Inhibitors for Pancreatic Cancer Therapy
S.NO	Chemokine	Chemokine Inhibitor	Study Organism	Experimental Study	Biological Effects	References
1.	CXCR2	Anti-CXCR2 antibody	BxPC-3 cell line	Secreted CXC protein levels	Inhibition of neovascularization	[89]
		CCR2 inhibitor PF-04136309 in combination with Folfirinox chemotherapy (oxaliplatin and irinote-can plus leucovorin and fluorouracil)	Human subjects with borderline resectable and locally advanced pancreatic cancer	Single-centre, open-label, dose-finding, non-randomised, phase 1b trial	Objective tumor response, with local tumor control in 32 (97%) patients.	[90]
		AZ13381758 is a potent inhibitor of both murine and human CXCR2	KPC mice	Immunotherapy by CXCR2 Inhibition in pancreatic ductal adenocarcinoma	Cxcr2 deficiency in KPC mice, Ly6G+ cell depletion, or CXCR2 inhibition suppresses metastasis in PDAC and enhance response to chemotherapeutics and immunotherapy to prolong survival.	[87]
		CXCR2 inhibitor repertaxin and SB225002	Mice bearing autochthonous PDAC. Ptf1acre/+; LSL-KrasG12D/+; Tgfbr2flox/flox	NF-κB inhibitor SC-514 (an IκB kinase-2 inhibitor) showed significant suppression of the CXCL1 and −5 expression	CXCR2 inhibitors repertaxin inhibited the PDAC–induced CTGF upregulation and tumor growth and exhibited antitumor effects in Ptf1acre/+; LSL-KrasG12D/+; Tgfbr2flox/flox PDAC mice	[91]
2.	CCR5	-	Human and mouse	Human pancreatic adenocarcinoma and a murine pancreatic tumor model (Pan02)	Reduction of T reg cells migration to tumors	[92]
3.	CXCL12	AMD3100, an inhibitor of chemokine (C-X-C motif) receptor 4, a CXCL12 receptor,	KPCD (LSL-KrasG12D/+; LSL-Tp53R172H/+; Pdx-1-Cre; FAP-DTR) mice, pancreatic cancer cell lines derived from tumors arising in KPC mice (TB32964, K8484), LL2 cell line expressing chicken OVA (LL2/OVA)	Targeting CXCL12 with anti–PD-L1 immunotherapy in pancreatic cancer	Revealed antitumor effects and greatly diminished cancer cells	[93]
4.	CXCR4	Zerumbone inhibitor of CXCR4	PANC-1 (pancreatic duct cell carcinoma), PANC-28 (pancreatic carcinoma), MIA PaCa-2 (pancreatic carcinoma), AsPC-1 (pancreatic adenocarcinoma)	Zerumbone, a component of subtropical ginger (Zingiber zerumbet), as a regulator of CXCR4 expression leading to inhibition of CXCL12-induced invasion of pancreatic tumor Cells	Suppression of CXCR4 NF-κB, inhibition of CXCL12-induced invasion of pancreatic cancer cells	[94]
5.	CCL21	Recombinant murine CCL21	C57BL/6	CCL21 mediated anti-tumor cellular immunity	Intratumoral injection of CCL21 into pancreatic tumors reduced the growth of distant tumors and treated tumors, immune cell infiltration of the tumor mass, delayed growth of treated tumors, and generate a tumor-specific cellular immune response	[95]
6.	CXCL2	Triptonide	Patu8988 and Panc1 cancer cells and in vivo mouse model of matrigel assay	Pancreatic cancer cell-mediated vasculogenesis	Inhibition of CXCL2 via reduction of gene promoter activity and suppresses pancreatic cancer cell-mediated tumor vasculogenic mimicry by reducing tumor cell migration and invasion and inhibiting expression of VE-cadherin and CXCL2	[96]