Abstract: A drilling head for a tubular shank having an inside diameter and threads may comprise an axial body comprising a duct exiting through a first end; threads adjacent the first end corresponding to the threads on the shank and aligning the duct with the shank inside diameter; a bore from an outer surface of the body to the duct; and two axially extending approximately parallel and offset surfaces adjacent a second end; and an insert affixed between the offset surfaces, the insert comprising: a first face at least partially contacting one offset surface and a second face at least partially contacting the other offset surface; one or more cutting edges adjacent the first face, the second face, or both; and a cutting lip adjacent one or more cutting edges.

Abstract: A drilling head for a tubular shank having an inside diameter and threads may comprise an axial body comprising a duct exiting through a first end; threads adjacent the first end corresponding to the threads on the shank and aligning the duct with the shank inside diameter; a bore from an outer surface of the body to the duct; and two axially extending approximately parallel and offset surfaces adjacent a second end; and an insert affixed between the offset surfaces, the insert comprising: a first face at least partially contacting one offset surface and a second face at least partially contacting the other offset surface; one or more cutting edges adjacent the first face, the second face, or both; and a cutting lip adjacent one or more cutting edges.

Abstract: A drilling head for a tubular shank having an inside diameter and threads may comprise an axial body comprising a duct exiting through a first end; threads adjacent the first end corresponding to the threads on the shank and aligning the duct with the shank inside diameter; a bore from an outer surface of the body to the duct; and two axially extending approximately parallel and offset surfaces adjacent a second end; and an insert affixed between the offset surfaces, the insert comprising: a first face at least partially contacting one offset surface and a second face at least partially contacting the other offset surface; one or more cutting edges adjacent the first face, the second face, or both; and a cutting lip adjacent one or more cutting edges.

Abstract: Aspects of the present invention provide compositions comprising a sulfur containing compound and a compound of the formula (I); and also provide methods of their preparation and use.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: A drilling head for a tubular shank having an inside diameter and threads may comprise an axial body comprising a duct exiting through a first end; threads adjacent the first end corresponding to the threads on the shank and aligning the duct with the shank inside diameter; a bore from an outer surface of the body to the duct; and two axially extending approximately parallel and offset surfaces adjacent a second end; and an insert affixed between the offset surfaces, the insert comprising: a first face at least partially contacting one offset surface and a second face at least partially contacting the other offset surface; one or more cutting edges adjacent the first face, the second face, or both; and a cutting lip adjacent one or more cutting edges.

Abstract: A drilling head for a tubular shank having an inside diameter and threads may comprise an axial body comprising a duct exiting through a first end; threads adjacent the first end corresponding to the threads on the shank and aligning the duct with the shank inside diameter; a bore from an outer surface of the body to the duct; and two axially extending approximately parallel and offset surfaces adjacent a second end; and an insert affixed between the offset surfaces, the insert comprising: a first face at least partially contacting one offset surface and a second face at least partially contacting the other offset surface; one or more cutting edges adjacent the first face, the second face, or both; and a cutting lip adjacent one or more cutting edges.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: Provided herein, inter alia, are solid forms of geldanamycin analogs, pharmaceutical compositions comprising a geldanamycin analog and a crystallization inhibitor, methods of making and using such compositions. Additionally, provided are methods for the treatment of cancer, a neoplastic disease state and/or a hyperproliferative disorder, and methods of inhibiting Heat Shock Protein 90 (“Hsp90”).

Abstract: Amorphous, polymorphic, and solvated forms of 17-amino geldanamycin are disclosed. These compounds are particularly useful for the treatment of cancer, a neoplastic disease state and/or a hyperproliferative disorder, and inhibiting Heat Shock Protein 90 (“Hsp90”).

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: The present invention provides compositions and methods for modulating smoothened-dependent pathway activation. The present invention provides analogs of cyclopamine that can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, Ptc loss-of-function or smoothened gain-of-function mutations. The compounds of the present invention are particularly useful in treating cancers.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: Aspects of the present invention provide compositions comprising a sulfur containing compound and a compound of the formula (I); and also provide methods of their preparation and use.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: The present invention provides compositions and methods for modulating smoothened-dependent pathway activation. The present invention provides analogs of cyclopamine that can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, Ptc loss-of-function or smoothened gain-of-function mutations. The compounds of the present invention are particularly useful in treating cancers.

Abstract: Provided herein, inter alia, are solid forms of geldanamycin analogs, pharmaceutical compositions comprising a geldanamycin analog and a crystallization inhibitor, methods of making and using such compositions. Additionally, provided are methods for the treatment of cancer, a neoplastic disease state and/or a hyperproliferative disorder, and methods of inhibiting Heat Shock Protein 90 (“Hsp90”).

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

Abstract: The present invention provides compositions and methods for modulating smoothened-dependent pathway activation. The present invention provides analogs of cyclopamine that can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, Ptc loss-of-function or smoothened gain-of-function mutations. The compounds of the present invention are particularly useful in treating cancers.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.