Methods of treating triple negative breast cancer (TNBC) using antibodies against p40 monomer are described herein. In some aspects, methods of treatment for TNBC include administration of antibodies against p40 monomer or administration of antibodies against p40 monomer in combination with a binding peptide such as TLR2-interacting domain of MyD88 (TIDM) peptide or NEMO-binding domain (NBD) peptide. Methods of treating other cancers using antibodies against p40 monomer in combination with a binding peptide such as TIDM peptide or NBD peptide are described herein.

A method is disclosed of treating pain with senicapoc, a potent Ca.sup.2+-activated K.sup.+ channel, K.sub.Ca3.1 antagonist in CNS-resident microglia. Senicapoc is shown to cause in a decrease of IL-1β and NO release from microglia cells vivo and in vitro. Because of contribution of K.sub.Ca3.1 to neuropathological processes, senicapoc is useful in the treatment of chronic, neuropathic, visceral, and inflammatory pain and the reversal of tactile allodynia.

A method is disclosed of treating pain with senicapoc, a potent Ca.sup.2+-activated K.sup.+ channel, K.sub.Ca3.1 antagonist in CNS-resident microglia. Senicapoc is shown to cause in a decrease of IL-1β and NO release from microglia cells vivo and in vitro. Because of contribution of K.sub.Ca3.1 to neuropathological processes, senicapoc is useful in the treatment of chronic, neuropathic, visceral, and inflammatory pain and the reversal of tactile allodynia.

The invention relates to peptide dimer compounds and peptide monomer compounds that potently inhibit binding of α4β7 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, possess high selectivity against α4β1 binding, and have high stability under gastrointestinal conditions.

Cis-tetrahydro-spiro(cyclohexane-1,1′-pyrido[3,4-b]indole)-4-amine compounds which act on the nociceptin/ORL-1 receptor system as well as on the μ-opioid receptor system and which are distinguished in particular by selective effectiveness in the treatment of chronic pain, such as inflammatory pain, visceral pain, tumour pain, and neuropathic pain, without at the same time developing pronounced effectiveness against acute, nociceptive pain.

The present invention is directed to pharmaceutical compositions of effective amounts of NMDA receptor antagonists and preservative for the administration to a patient in need of effective analgesia and anesthesia. The compositions of the invention advantageously do not cause any significant neurotoxicity. The preferred NMDA receptor antagonist is ketamine. The preferred preservative is benzalkonium chloride.

Provided are an isoindoline derivative, intermediate, preparation method, pharmaceutical composition and use thereof. The isoindoline derivative and the pharmaceutical composition thereof can regulate the production or activity of immunological cytokines, thus effectively treating cancer and inflammatory disease.

##STR00001##

Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Na.sub.V1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Na.sub.V1.7 and/or Na.sub.V1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

There are provided compounds of formula I, ##STR00001##
wherein R.sup.1 to R.sup.5, X.sup.1, X.sup.2, Ar, L, A, A.sup.1, E and G have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

The present disclosure relates to substituted heterocyclic derivative therapeutic compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of diseases mediated by aberrant cell signalling, such as inflammatory disorders, cancer and neoplastic disease.