PHENFORMIN

US Previously Marketed

First approved in 1959

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H15N5
Molecular Weight	205.26
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc(cc1)CCNC(=N)NC(=N)N

InChI

InChIKey=ICFJFFQQTFMIBG-UHFFFAOYSA-N

InChI=1S/C10H15N5/c11-9(12)15-10(13)14-7-6-8-4-2-1-3-5-8/h1-5H,6-7H2,(H6,11,12,13,14,15)

HIDE SMILES / InChI

Molecular Formula	C10H15N5
Molecular Weight	205.26
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.druglib.com/activeingredient/phenformin/ | https://www.ncbi.nlm.nih.gov/pubmed/9848705 | https://www.ncbi.nlm.nih.gov/pubmed/20444419 | https://www.ncbi.nlm.nih.gov/pubmed/25511514

Phenformin is a biguanide hypoglycemic agent with actions and uses similar to those of metformin. It activates AMP-activated protein kinase (AMPK) and inhibits mTORC1 signaling. Phenformin used for the treatment of diabetes. Phenformin was removed from the U.S. market 20 years ago because of a high incidence of lactic acidosis. Risk factors for the development of lactic acidosis include renal deficiency, hepatic disease, cardiac disease, and drug interaction such as cimetidine. Phenformin exerts potential anti-neoplastic action.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
AMP-activated protein kinase, AMPK 16 Target ID: CHEMBL2096907 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29245964 \| https://www.ncbi.nlm.nih.gov/pubmed/14976552	Activator 1343
Monoamine oxidase A 48 Target ID: CHEMBL1951 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24307270	Inhibitor 7728	41.0 µM [IC50]
Sulfonylurea receptors; K-ATP channels 11 Target ID: CHEMBL2095152 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20188727	Blocker 511
Mammalian target of Rapamycin (mTORC1) 22 Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20444419	Inhibitor 7728

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 144 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29245964	Primary	Preclinical	Unknown Approved Use Unknown
Breast cancer 411 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26114294	Primary	Preclinical	Unknown Approved Use Unknown
Type 2 diabetes mellitus 240 Sources: https://www.ndrugs.com/?s=phenformin http://www.druglib.com/activeingredient/phenformin/ https://www.drugs.com/international/phenformin.html	Primary	Approved 8043	INFORMIN Approved Use For the treatment of type II diabetes mellitus.
Melanoma 81 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28433543	Primary	Phase I 409	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1133221/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENFORMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
81% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1133221/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENFORMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea Vomiting Anxiety Agitation Polydipsia Polyuria Increased appetite Tachycardia Tachypnea Lactic acidosis Hypoglycemia Hypokalemia Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
400 mg 2 times / day multiple, oral (max) Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic	Disc. AE: Lactic acidosis... AEs leading to discontinuation/dose reduction: Lactic acidosis Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic

AEs

AE	Significance	Dose	Population
Agitation	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Anxiety	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Hypoglycemia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Hypokalemia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Increased appetite	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Lactic acidosis	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Nausea	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Polydipsia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Polyuria	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Tachycardia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Tachypnea	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Vomiting	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Lactic acidosis	Disc. AE	400 mg 2 times / day multiple, oral (max) Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1118	supressor 9

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1400 hOCT1 4

Drug as victim

Target	Modality	Activity
CYP2D6 1118	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/1293869/	yes
P-gp 1400	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/26797108/	yes
hOCT1 4	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19768675/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	supressor 9 Sources: https://pubmed.ncbi.nlm.nih.gov/23716168/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34451	https://www.001chemical.com/chem/834-28-6
3B Scientific (Wuhan) Corp	3B2-0951	http://www.3bsc.com/index/pro_info.php?id=41856
AA Blocks	AA00ID7X	https://www.aablocks.com/goods/Goods/detail?id=AA00ID7X
AHH Chemical co.,ltd	MT-57838	http://www.ahhchemical.com/product/MT-57838.html
AK Scientific, Inc. (AKSCI)	65624	http://www.aksci.com/item_detail.php?cat=65624
Aaron Chemicals	AR00IDZP	http://www.aaronchem.com/834-28-6
AbMole Bioscience	M5336	http://www.abmole.com/products/phenformin-hcl.html
Acadechem	ACDS-067766	http://www.acadechemical.com/product/142465
Achemtek	0104-024279	http://www.achemtek.com/834-28-6
Acorn PharmaTech	ACN-048751	http://www.acornpharmatech.com/
Adooq BioScience	A10717	https://www.adooq.com/phenformin-hydrochloride.html
Alfa Chemistry	834-28-6	https://www.alfa-chemistry.com/phenformin-hydrochloride-cas-834-28-6-item-293833.htm
Ambeed	A247771	https://www.ambeed.com/products/834-28-6.html
ApexBio Technology	B1373	http://www.apexbt.com/phenformin-hcl.html
Ark Pharm	AK307682	http://www.arkpharminc.com/products/834-28-6.html
Aurora Fine Chemicals LLC	A13.140.994	http://online.aurorafinechemicals.com/info?ID=A13.140.994
Aurum Pharmatech LLC	KM2166	http://www.Aurumpharmatech.com/Product/ProductDetails/KM2166
BLD Pharm	BD147439	http://www.bldpharm.com/products/834-28-6.html
BOC Sciences	114-86-3	https://buildingblock.bocsci.com/product/n-phenethylbiguanide-cas-114-86-3-295939.html
BOC Sciences	834-28-6	https://www.bocsci.com/phenformin-hcl-cas-834-28-6-item-84-78129.html
BioChemPartner	BCP21997	http://www.biochempartner.com/834-28-6-BCP21997
BioCrick	BCC4362	http://www.biocrick.com/Phenformin-HCl-BCC4362.html
BioSynth	W-104144	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-104144.html
CSNpharm	CSN11690	https://www.csnpharm.com/products/phenformin-hydrochloride.html
Chem Scene	CS-1850	http://www.chemscene.com/834-28-6.html
ChemMol	30110994	http://www.chemmol.com/chemmol/30110994.html
ChemMol	49400581	http://www.chemmol.com/chemmol/49400581.html
ChemShuttle	141584	http://www.chemshuttle.com/catalogsearch/result/?q=834-28-6&cat=
Chemspace	CSSB00000014702	https://chem-space.com/CSSB00000014702
Clearsynth	CS-O-11710	https://www.clearsynth.com/en/CSO11710.html
Combi-Blocks	QA-6093	http://www.combi-blocks.com/cgi-bin/find.cgi?QA-6093
DC Chemicals	DC8990	http://www.dcchemicals.com/product_show-Phenformin_hydrochloride.html
Finetech	FT-0603518	http://www.finetechnology-ind.com/prod/detail/pub/834-28-6.html
LGC Standards	DRE-C16004500	https://www.lgcstandards.com/US/en/p/DRE-C16004500
LGC Standards	LGCFOR1574.00	https://www.lgcstandards.com/US/en/p/LGCFOR1574.00
LGC Standards	MM1574.00	https://www.lgcstandards.com/US/en/p/MM1574.00
Lab Network	LN00223478	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00223478
Matrix Scientific	157511	https://www.matrixscientific.com/157511.html
MedChem Express	HY-16397A	https://www.medchemexpress.com/phenformin-hydrochloride.html
MolPort	MolPort-000-715-918	https://www.molport.com/shop/molecule-link/MolPort-000-715-918
MolPort	MolPort-044-175-502	https://www.molport.com/shop/molecule-link/MolPort-044-175-502
Molcore	MC34451	https://www.molcore.com/product/834-28-6
MuseChem	A000869	https://www.musechem.com/product/A000869.html
OChem	4785	http://www.ocheminc.com/index.php?act=psearch&pid=34P286
Oakwood	245710	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=167560&ExtHyperLink=1
Selleck Chemicals	S2542	http://www.selleckchem.com/products/Phenformin-hydrochloride.html
Sigma-Aldrich	P7045_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/p7045?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	PHR1573_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/phr1573?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S052109	http://www.sinfoobiotech.com/product/1055507
Smolecule	S539401	http://www.smolecule.com/products/s539401
THE BioTek	bt-279431	https://www.thebiotek.com/product/inhibitors/bt-279431
VladaChem	VL272143-100G	https://www.vladachem.com/product.php?products=834-28-6
Yuhao Chemical	RT19039	http://www.chemyuhao.com/834-28-6.html
abcr GmbH	AB357549	http://www.abcr.de/shop/en/AB357549
abcr GmbH	AB376791	http://www.abcr.de/shop/en/AB376791
eNovation Chemicals	K96005	https://www.enovationchem.com/ProductDetails.asp?ProductID=K96005
iChemical	EBD40961	http://www.ichemical.com/products/834-28-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-2649903903	https://mcule.com/MCULE-2649903903/

PubMed

Title	Date	PubMed
Phenformin-induced lactic acidosis in an older diabetic patient: a recurrent drama (phenformin and lactic acidosis).	2006 Apr	16567854
LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.	2006 Dec 22	17083919
Use of microarray biomarkers to identify longevity therapeutics.	2006 Feb	16441842
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.	2006 Jan 25	16437448
Phosphorylation and 14-3-3 binding of Arabidopsis trehalose-phosphate synthase 5 in response to 2-deoxyglucose.	2006 Jul	16771775
AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of Akt and glycogen synthase kinase-3.	2006 May 28	16620785
Solid phase extraction--non-aqueous capillary electrophoresis for determination of metformin, phenformin and glyburide in human plasma.	2006 Oct 20	16787767
Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase gamma3-subunit differentially regulates glycogen accumulation.	2006 Sep	16638825
[Diabetic lactic acidosis].	2006 Sep 28	17022521
The phase shift hypothesis for the circadian component of winter depression.	2007	17969866
Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae.	2007	17708636
Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.	2007 Apr	17339833
The role of AMPK and mTOR in nutrient sensing in pancreatic beta-cells.	2007 Apr 6	17287212
The role of mitochondria in protection of the heart by preconditioning.	2007 Aug	17631856
Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.	2007 Aug	17603555
Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography-tandem mass spectrometry.	2007 Feb	17221919
Protein kinase CK2 acts as a signal molecule switching between the NDPK-A/AMPK alpha1 complex and NDPK-B.	2007 Jan	17135357
Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration.	2007 Jul	17369473
Simultaneous determination of metformin and rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry with electrospray ionization: application to a pharmacokinetic study.	2007 Jul 1	17459785
Comparison of the kinetic characteristics of inhibitory effects exerted by biguanides and H2-blockers on human and rat organic cation transporter-mediated transport: Insight into the development of drug candidates.	2007 Jun	17614008
Regulation of the atherogenic properties of vascular smooth muscle proteoglycans by oral anti-hyperglycemic agents.	2007 Mar-Apr	17331859
Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR.	2007 Oct 15	17617058
Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions.	2007 Oct 28	17963526
Cellular and molecular mechanisms in the long-term action of antidepressants.	2008	19170396
Cross-Species Differential Plasma Protein Binding of MBX-102/JNJ39659100: A Novel PPAR-gamma Agonist.	2008	18815616
[Cardiovascular risk and cardiometabolic risk: an epidemiological evaluation].	2008 Apr	18773746
Comparison of gene expression changes induced by biguanides in db/db mice liver.	2008 Aug	18670165
Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine kinase inhibitor sunitinib.	2008 Dec	18815214
Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle.	2008 Dec	18796617
Older age and phenformin therapy: a dangerous association.	2008 Dec	18415028
Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro.	2008 Dec 1	18817800
Hazards posed by a banned drug--phenformin is still hanging around.	2008 Feb	18239244
Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators.	2008 Jan 15	17995453
Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice.	2008 Jun 1	18387000
[Experimental studies on hypoglycemic effects of total flavonoid from Toona sinensis].	2008 Nov	19260289
AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers.	2008 Nov	18723760
Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance.	2008 Sep	18577554
Uncoupling of the LKB1-AMPKalpha energy sensor pathway by growth factors and oncogenic BRAF.	2009	19274086
AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease.	2009 Apr	19275766
Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing.	2009 Apr 17	19468337
High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus.	2009 Apr 21	19349317
Simultaneous determination of anti-diabetes/anti-obesity drugs by LC/PDA, and targeted analysis of sibutramine analog in dietary supplements by LC/MS/MS.	2009 Dec	19475544
Mechanistic insight into control of CFTR by AMPK.	2009 Feb 27	19095655
Are animal models predictive for humans?	2009 Jan 15	19146696
C-terminal phosphorylation of LKB1 is not required for regulation of AMP-activated protein kinase, BRSK1, BRSK2, or cell cycle arrest.	2009 Jan 2	18854318
Quasi-equilibrium analysis of the ion-pair mediated membrane transport of low-permeability drugs.	2009 Jul 1	19264104
Regulation of Cl(-) secretion by AMPK in vivo.	2009 Mar	18752001
Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline.	2009 May	19238488
Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation.	2009 May 15	19435925
Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.	2009 Sep	19502419

Patents

Sample Use Guides

In Vivo Use Guide

200-400 mg bid.

Route of Administration: Oral

In Vitro Use Guide

To evaluate the underlying mechanism of growth inhibition by phenformin, the cell cycle profile was analyzed after treating the SKOV3, Hey and IGROV-1 cell lines with varying doses (0.01-2.5 mM) of phenformin for 24 hours. Phenformin induced G0/G1 cell cycle arrest and reduced S phase in the Hey and SKOV3 OC cell lines and increased G2 phase in the IGROV-1 OC cell line in a dose-dependent manner.

Substance Class	Chemical Created by `admin` on `Sat Jun 26 11:21:03 UTC 2021` Edited by `admin` on `Sat Jun 26 11:21:03 UTC 2021`
Record UNII	DD5K7529CE
Record Status	`Validated (UNII)`
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Name

Type

Language

PHENFORMIN

Official Name

English

PHENFORMIN [INN]

Common Name

English

PHENFORMIN [MI]

Common Name

English

PHENFORMIN [HSDB]

Common Name

English

PHENFORMIN [WHO-DD]

Common Name

English

IMIDODICARBONIMIDIC DIAMIDE, N-(2-PHENYLETHYL)-

Systematic Name

English

PHENFORMIN [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QA10BD01