Chemocentryx, Inc.

Zhenhua Miao

Thomas J Schall

Rajinder Paul Singh

Zheng Wei

Brett Anthony Premack

Daniel J Dairaghi

Michael R Hanley

Jennifa Gosling

Maureen Howard

Israel Charo

Jennifer M Burns

Dale John Talbot

Robert Berahovich

James J Campbell

Maureen C Howard

Karen Ebsworth

Shijie Li

Mark Penfold

Bretton Summers

Christine Marie Janson

A method of treating focal segmental glomerulosclerosis with a compound of Formula I is provided. FSGS may be primary (no known cause) or secondary. The secondary FSGS may be associated with infections or viruses such as HIV, diseases such as sickle cell disease or lupus, toxins or drugs such as anabolic steroids, heroin or pamidronate, nephron loss and hyperfiltration, such as with chronic pyelonephritis and reflux, morbid obesity, or diabetes mellitus.

Method of treating focal segmental glomerulosclerosis

Provided herein are methods of treating focal segmental glomerulosclerosis, said methods include administering to a subject in need thereof a therapeutically effective amount of a CCR2 antagonist. In some embodiments, the CCR2 antagonist is used in monotherapy. In some embodiments, the CCR2 antagonist is used in combination therapy. In some embodiments, the additional therapeutic agent is a RAAS blocker and/or an endothelin receptor inhibitor. The CCR2 antagonist may have the structure of formula (I). 

Treatment of focal segmental glomerulosclerosis with CCR2 antagonists

A method of treating liver fibrosis with CCR2 antagonists is provided. The liver fibrosis may be associated with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), emerging cirrhosis, non-cirrhotic hepatic fibrosis, type 2 diabetes mellitus (T2DM) or metabolic syndrome (MS).

Method of treating liver fibrosis

Method of Treating Focal Segmental Glomerulosclerosis

The present disclosure is drawn to the combination therapy of a Chemokine Receptor 2 (CCR2) antagonist and a PD-1 and/or PD-L1 inhibitor in the treatment of cancer.

Combination therapy using a chemokine receptor 2 (CCR2) antagonist and a PD-1/PD-L1 inhibitor

The inventors have discovered that a CK&#x3b2;8-1 truncation variant, CK&#x3b2;8-1 (25-116), is a bifunctional ligand for two distinct GPCRs, chemokine receptor CCR1 and formyl peptide receptor like 1 (FPRL1). Hence, the inventors have discovered that, in addition to its functional activity on CCR1, CK&#x3b2;8-1(25-116) is also a functional ligand for the GPCR receptor FPRL1 that is involved in inflammatory reactions and innate immunity by recruiting monocytes and neutrophils. In addition, the inventors have discovered an alternatively spliced exon of CK&#x3b2;8-1, named SHAAGtide. SHAAGtide, along with its parent chemokine CK&#x3b2;8-1 (25-116), is fully functional on both monocytes and neutrophils that are known to express FPRL1. This application relates generally to enhancing immune responses. Such immune responses may be elicited by vaccine administration. Compositions and methods for inducing or enhancing an immune response to an antigen are provided. The compositions and methods are useful for vaccine formulations for therapeutic and prophylactic use (immunization) and for production of antibodies.

Compositions useful as ligands for the formyl peptide receptor like 1 receptor and methods of use thereof

Antibodies that bind CXCR7 epitopes, as well as methods of identifying CXCR7 modulators are described.

Antibodies that bind CXCR7 epitopes

Ligands of CCX-CKR2 and the biological role of CCX-CKR2 in cancer is described.

Compositions and methods for detecting and treating diseases and conditions related to chemokine receptors

Truncated chemokines lacking an N-terminal region that activate CCR1 and/or FPRL1 and compositions containing the truncated chemokines are provided. Methods of identifying agents that modulate CCR1 and/or FPRL1 activity either by modulating the production of the truncated chemokines or the ability of the truncated chemokines to activate CCR1 and/or FPRL1 are also disclosed. Methods using the truncated chemokines to inhibit or activate CCR1 and/or FPRL1 mediated biological activities are also disclosed.

Enzymatic activities in chemokine-mediated inflammation

The present invention provides methods for identifying an agent that specifically binds and/or modulates one topology of chemokine receptor but not a second topology of the receptor. Such agents are useful as therapeutics for diseases or conditions associated with a particular chemokine receptor topology. Moreover, the agents are useful for detecting a particular topology of a chemokine receptor, thereby diagnosing disease or predisposition for a disease. In addition, the agents are useful for identifying and isolating cells that express a particular topology of a chemokine receptor.

The present invention provides methods for identifying an agent that specifically binds and/or modulates one topology of a chemokine receptor but not a second topology of the receptor. Such agents are useful as therapeutics for diseases or conditions associated with a particular chemokine receptor topology. Moreover, the agents are useful for detecting a particular topology of a chemokine receptor, thereby diagnosing disease or predisposition for a disease. In addition, the agents are useful for identifying and isolating cells that express a particular topology of a chemokine receptor.

The present invention is directed to a modified cell migration assay allowing for improved identification and discrimination of chemokine receptor antagonists from non-specific blockers.

Growing community of inventors

San Jose, CA, United States of America

Zhenhua Miao