CCR

The CC class of chemokines consists of at least 28 members (CCL1-28) that signal through 10 known chemokine receptors (CCR1-10). CC chemokine receptors are expressed predominantly by T cells and monocyte-macrophages, cell types associated predominantly with chronic inflammation occurring over weeks or years.

106362-34-9
DAPTA
106362-34-9
1173022-16-6
1173022-16-6
BX 513 hydrochloride
1216540-18-9
YJC-10592
1226894-87-6
1228650-83-6
JNJ-41443532
1228650-83-6
B0084-457803
INCB3344
1262238-11-8
1313730-14-1
Teijin compound 1
1313730-14-1
1341224-83-6
PF-4136309
1341224-83-6
140926-75-6
NSC5844
140926-75-6
1780259-94-0
212790-31-3
CP-481715
212790-31-3
B0084-462270
BX 471
217645-70-0
233277-99-1
K-11777
233277-99-1
247580-43-4
SB 328437
247580-43-4
288262-96-4
BX471 hydrochloride
288262-96-4

Background


An Overview of CCR

Chemokine receptor (CCR) is a family of seven transmembrane protein receptors coupled with guanine nucleotide binding protein (G protein). Its ligand can be divided into CXC and CC receptors, which are one of the main auxiliary receptors of HIV-1 invading organism cells. The HIV-1 receptor antagonists targeting CCR5 have attracted more and more attention, including chemokine derivatives, non-peptide small molecular compounds, monoclonal antibodies, peptide compounds and so on. CCR5 is a receptor of intracellular B chemokines (RANTESU MIP-1A and MIP-1B). It regulates the migration, proliferation and immunity of T cells and monocytes / megafils, and is mainly expressed in memory resting T lymphocytes and monocytes. From a genetic point of view, multiple mutants in the CCR5 gene can effectively resist HIV virus infection and delay the deterioration of the disease.

Inhibition of CCR

Non-peptide small molecular compounds are the main antagonists of CCR without potential inflammatory response effect , which have the advantages of low cost of producing small molecular proteins and can be administered via intravenous injection, but also have the disadvantage of not down-regulating the expression of receptors. The inhibitory effect of CCR antagonists is also related to cell type and CCR concentration on cell surface. TAK-779 is the first CCR5 small molecule antagonist developed by Takeda Company in Japan. It is mainly used in the study of anti-HIV drugs targeting CCR5.

CCR and Diseases

CCR is used as coreceptor in the early stage of infection. Coreceptor CCR is the first target of HIV-1 infection. Different types of CCR antagonists have different blocking mechanisms. However, although coreceptor antagonists can effectively prevent HIV-1 infection and curb the prevalence of AIDS, the development of these inhibitors is also facing challenges. Long-term use of an inhibitor will eventually lead to resistance to HIV-1. Therefore, the development of more drug-resistant anti-HIV drugs, and the combination of drugs will be the main direction in the future treatment of AIDS.