Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula

##STR00001##

inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.

The present disclosure provides GLP-1R agonists, and compositions, methods, and kits thereof. Such compounds are generally useful for treating a GLP-1R mediated disease or condition in a human.

The present disclosure provides GLP-1R agonists, and compositions, methods, and kits thereof. Such compounds are generally useful for treating a GLP-1R mediated disease or condition in a human.

The invention provides compounds of formula (I), their pharmaceutically acceptable salts and prodrugs thereof for use in preventing, inhibiting or treating a disease caused by a mutation in the gene coding for hydroxymethylbilane synthase, in particular for preventing, inhibiting or treating acute intermittent porphyria: (I) wherein: A is selected from N and CR.sup.10 (wherein R.sup.10 is H, —NO.sub.2, C.sub.1-6 haloalkyl or —C(O)R.sup.17 in which R.sup.17 is H or C.sub.1-6 alkyl); Z is selected from N and CR.sup.9 (wherein R.sup.9 is H, halogen (e.g. F, Cl, Br or I) or —OR.sup.16 in which R.sup.16 is H, C.sub.1-6 haloalkyl, or optionally substituted C.sub.1-6 alkyl); L is selected from —CH.sub.2—, —C(O)—, —CH(OH)—, —C(O)—NR′—, and —NR′—C(O)— (wherein R′ is H or C.sub.1-3 alkyl, e.g. —CH.sub.3); R.sup.1 is H; R.sup.2 is selected from H, halogen (e.g. F, Cl, Br or I), —NR.sup.11R.sup.12 (wherein R.sup.11 and R.sup.12 are independently selected from H and C.sub.1-6 alkyl or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered saturated ring), and —OR13 (wherein R.sup.13 is H or C.sub.1-6 alkyl); R.sup.3 is selected from H, —CH.sup.2OH and —C(O)R.sup.14 (wherein R.sup.14 is H or C.sub.1-6 alkyl); R.sup.4 is selected from H, halogen (e.g. F, Cl, Br or I) and —OR.sup.15 (where R.sup.15 is H or C.sub.1-6 alkyl); R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is selected from H, —NO.sub.2 and halogen (e.g. F, Cl, Br or I); R.sup.7 is H; and R.sup.8 is selected from H, C.sub.1-6 alkyl, and halogen (e.g. F, Cl, Br or I); or wherein: R.sup.7 and R.sup.8 together with the intervening ring carbon atoms form an unsaturated ring, preferably an aryl ring.

##STR00001##

The present invention provides a pharmaceutical combination comprising a CRAF inhibitor plus (i) an ERK inhibitor or (ii) a MEK inhibitor, for use in the treatment of non-small cell lung cancer (NSCLC) where the carcinoma cells of the NSCLC harbor a mutation of BRAF other than the BRAF V600E-mutant, and related invention aspects. The present invention also provides dosages and dosage regimens of a CRAF inhibitor with an ERK inhibitor or with trametinib for use in the treatment of BRAF V600 mutant (e.g. BRAF V600E mutant) NSCLC.

The present invention provides a pharmaceutical combination comprising a CRAF inhibitor plus (i) an ERK inhibitor or (ii) a MEK inhibitor, for use in the treatment of non-small cell lung cancer (NSCLC) where the carcinoma cells of the NSCLC harbor a mutation of BRAF other than the BRAF V600E-mutant, and related invention aspects. The present invention also provides dosages and dosage regimens of a CRAF inhibitor with an ERK inhibitor or with trametinib for use in the treatment of BRAF V600 mutant (e.g. BRAF V600E mutant) NSCLC.

The present invention provides a pharmaceutical combination comprising a CRAF inhibitor plus (i) an ERK inhibitor or (ii) a MEK inhibitor, for use in the treatment of non-small cell lung cancer (NSCLC) where the carcinoma cells of the NSCLC harbor a mutation of BRAF other than the BRAF V600E-mutant, and related invention aspects. The present invention also provides dosages and dosage regimens of a CRAF inhibitor with an ERK inhibitor or with trametinib for use in the treatment of BRAF V600 mutant (e.g. BRAF V600E mutant) NSCLC.

The disclosure relates generally to improvements in the treatment of pruritus, atopic dermatitis (AD), and associated symptoms with tradipitant. More particularly, it relates to a method for increasing the likelihood of achieving optimal therapeutic response in the treatment of an AD patient, where the AD patient is one for whom a potential therapy of choice may include the administration of an amount of an NK-1 antagonist, e.g. tradipitant effective to treat the patient's AD.

Provided are compositions and methods for treating osteoarthritis including intra-articular administration of a compound of Formula (I) ##STR00001##
including amorphous and polymorph forms thereof.

Provided are compositions and methods for treating osteoarthritis including intra-articular administration of a compound of Formula (I) ##STR00001##
including amorphous and polymorph forms thereof.