NPASS Compound

Natural Product: NPC300596

Natural Product ID	NPC300596
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Indirubin
IUPAC Name	(3Z)-3-(3-oxo-1H-indol-2-ylidene)-1H-indol-2-one
Synonyms	Indirubin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1276127
PubChem CID	5318433
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0001146] Indolines

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 30 33 0 0 0 0 0 0 0 0999 V2000 -0.0241 2.0593 0.3415 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6555 1.0667 0.1937 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3266 -0.3295 0.0578 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8446 -0.9176 0.0584 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1073 -2.3553 -0.0858 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3680 -2.5573 -0.0376 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.0501 -1.3083 0.1386 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1399 -0.2642 0.2031 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5691 1.0076 0.3676 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9374 1.2598 0.4721 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8352 0.2167 0.4071 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3988 -1.0793 0.2394 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1587 -3.3276 -0.2464 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5472 -1.0767 -0.0931 N 0 0 0 0 0 0 0 0 0 0 0 0 2.6179 -0.1514 -0.0508 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1411 1.1242 0.1169 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9748 2.2211 0.1914 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3569 2.0643 0.0967 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8362 0.7951 -0.0704 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0069 -0.3051 -0.1456 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9619 1.8632 0.4282 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2705 2.2766 0.6031 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8782 0.4288 0.4889 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1397 -1.8755 0.1929 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2716 -4.2661 0.1594 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6305 -2.0873 -0.2095 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5903 3.2157 0.3229 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9673 2.9519 0.1606 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8919 0.6498 -0.1456 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4118 -1.2997 -0.2782 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 5 13 1 0 3 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 16 2 1 0 8 4 1 0 20 15 1 0 12 7 1 0 9 21 1 0 10 22 1 0 11 23 1 0 12 24 1 0 13 25 1 0 14 26 1 0 17 27 1 0 18 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	CRDNMYFJWFXOCH-YPKPFQOOSA-N
Standard InCHI	InChI=1S/C16H10N2O2/c19-15-10-6-2-4-8-12(10)17-14(15)13-9-5-1-3-7-11(9)18-16(13)20/h1-8,17H,(H,18,20)/b14-13-
SMILES	O=C1/C(=C2/C(=Nc3c2cccc3)O)/Nc2c1cccc2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	262.07	Volume:	266.912 ? Van der Waals volume.
Dense:	0.982	LogP:	2.142 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.073 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.464 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	22.0
TPSA:	61.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.716	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.592	Fsp³:	0.0
MCE-18:	40.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.814	Fluc inhibitor:	0.941 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.413 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.297 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.096	Promiscuous compounds:	0.355

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.532	MDCK Permeability:	-4.69
Pgp-inhibitor:	0.999	Pgp-substrate:	0.0
PAMPA:	0.247 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.394
20% Bioavailability (F20%):	0.002	30% Bioavailability (F30%):	0.21
50% Bioavailability (F50%):	0.063

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.005
Plasma Protein Binding (PPB):	97.867%	Volume Distribution (VD):	-0.207
Fu:	1.265% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.964
OATP1B3 inhibitor:	0.98	BCRP inhibitor:	0.0
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.912	CYP1A2-substrate:	0.516
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.452
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.707
CYP2D6-inhibitor:	0.141	CYP2D6-substrate:	0.233
CYP3A4-inhibitor:	0.022	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.948
HLM stability:	0.916 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

0.792

Half-life (T1/2):

1.19

ADMET: Toxicity

hERG Blockers:	0.084	hERG Blockers (10um):	0.234
Human Hepatotoxicity (H-HT):	0.985	Drug-induced Liver Injury (DILI):	0.985
AMES Toxicity:	0.802	Rat Oral Acute Toxicity:	0.645
Maximum Recommended Daily Dose:	0.437	Skin Sensitization:	0.981
Carcinogencity:	0.815	Eye Corrosion:	0.001
Eye Irritation:	0.943	Respiratory Toxicity:	0.681
Drug-induced Neurotoxicity:	0.548	Ototoxicity:	0.579
Hematotoxicity:	0.715	Drug-induced Nephrotoxicity:	0.884
Genotoxicity:	0.948	RPMI-8226 Immunitoxicity:	0.025
A549 Cytotoxicity:	0.019	Hek293 Cytotoxicity:	0.195
BCF:	1.029 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.896 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.591 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.333 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11678654]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15787451]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	Roots	Anhui, China	n.a.	PMID[22694318]
NPO8274	Geijera parviflora	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23848189]
NPO6485	Spiraea japonica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24684844]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	leaf	n.a.	PMID[26434122]
NPO8274	Geijera parviflora	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6485	Spiraea japonica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6485	Spiraea japonica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1007	Crotalaria paniculata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6485	Spiraea japonica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO30657	Lndigofera tinctoria	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4520	Allium macrostemon	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1007	Crotalaria paniculata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6485	Spiraea japonica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8274	Geijera parviflora	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15101	Tricholoma panaeolum	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	79
Change in IC50	2
Potency	18
Inhibition	12
EC50	1
Activity	16
FC	1
MIC	1
ID50	1
Survival	1

Activity Type	# Activity
Individual protein	36
Cell line	44
Protein complex	20
Organism	7
Protein family	6
Unchecked	3
Protein-protein interaction	1
Single protein	1
Others	5
Non-molecular	9

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1371	Individual protein	Cyclin-dependent kinase 2	Homo sapiens	IC50	=	2200.0	nM	PMID[12672248]
NPT1564	Individual protein	Malate dehydrogenase	Thermus thermophilus	IC50	=	30000.0	nM	PMID[12672248]
NPT1650	Individual protein	Tyrosine-protein kinase receptor FLT3	Homo sapiens	IC50	>	10000.0	nM	PMID[20153646]
NPT2741	Individual protein	Pyruvate kinase	Leishmania mexicana	Potency	=	17782.8	nM	PubChem BioAssay data set
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT1423	Individual protein	Cyclin-dependent kinase 1	Homo sapiens	IC50	=	10000.0	nM	PMID[20810192]
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	125.9	nM	PubChem BioAssay data set
NPT3230	Individual protein	Serine/threonine-protein kinase 17B	Homo sapiens	IC50	>	10000.0	nM	PMID[27106709]
NPT1438	Individual protein	Insulin-like growth factor I receptor	Homo sapiens	IC50	>	1000000.0	nM	PMID[28557430]
NPT155	Individual protein	Aryl hydrocarbon receptor	Homo sapiens	EC50	=	0.2	nM	PMID[36274276]
NPT1509	Protein complex	Cyclin-dependent kinase 5/CDK5 activator 1	Homo sapiens	IC50	=	10000.0	nM	PMID[16854069]
NPT1509	Protein complex	Cyclin-dependent kinase 5/CDK5 activator 1	Homo sapiens	IC50	=	5000.0	nM	PMID[15163202]
NPT607	Individual protein	Beta-chymotrypsin	Homo sapiens	IC50	=	100000.0	nM	PMID[12672248]
NPT537	Individual protein	Ras-related protein Rab-9A	Homo sapiens	Potency	=	5623.4	nM	PubChem BioAssay data set
NPT4684	Individual protein	Protein-glutamine gamma-glutamyltransferase	Homo sapiens	IC50	>	100000.0	nM	PMID[21215619]
NPT1560	Protein complex	Cyclin-dependent kinase 4/cyclin D1	Homo sapiens	IC50	=	12000.0	nM	PMID[28557430]
NPT1509	Protein complex	Cyclin-dependent kinase 5/CDK5 activator 1	Homo sapiens	IC50	=	5500.0	nM	PMID[28557430]
NPT36	Individual protein	Tyrosine-protein kinase SRC	Homo sapiens	IC50	=	18000.0	nM	PMID[12672248]
NPT698	Individual protein	Regulator of G-protein signaling 4	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT67	Individual protein	Cholinesterase	Equus caballus	Inhibition	=	13.7	%	PMID[23062825]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-1.301	%	DOI[10.6019/CHEMBL4495564]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-7.59	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	60.61	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	19952.6	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	199.5	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	398.1	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	141.3	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	89.1	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	100.0	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	251.2	nM	PubChem BioAssay data set
NPT583	Individual protein	Inositol monophosphatase 1	Rattus norvegicus	Potency	=	3548.1	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	100000.0	nM	PubChem BioAssay data set
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	Inhibition	=	7.97	%	PMID[23062825]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	IC50	=	4.0	nM	PMID[26562543]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	IC50	=	600.0	nM	PMID[28557430]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	IC50	=	5.0	nM	PMID[27689729]
NPT1570	Protein complex	Cyclin-dependent kinase 1/cyclin B	Homo sapiens	IC50	=	10000.0	nM	PMID[14761195]
NPT1572	Protein family	Glycogen synthase kinase-3	Homo sapiens	IC50	=	1000.0	nM	PMID[16854069]
NPT1570	Protein complex	Cyclin-dependent kinase 1/cyclin B	Homo sapiens	IC50	=	6500.0	nM	PMID[15163202]
NPT1572	Protein family	Glycogen synthase kinase-3	Homo sapiens	IC50	=	2500.0	nM	PMID[15163202]
NPT56	Individual protein	Beta-lactamase AmpC	Escherichia coli K-12	Change in IC50	>	50.0	fold	PMID[12672248]
NPT56	Individual protein	Beta-lactamase AmpC	Escherichia coli K-12	Change in IC50	=	4.0	fold	PMID[12672248]
NPT197	Protein-protein interaction	Menin/Histone-lysine N-methyltransferase MLL	Homo sapiens	Potency	=	1122.0	nM	PubChem BioAssay data set
NPT1561	Protein complex	Cyclin-dependent kinase 1/cyclin B1	Homo sapiens	IC50	=	20000.0	nM	PMID[28557430]
NPT3944	Protein complex	Cyclin-dependent kinase 2/cyclin E1	Homo sapiens	IC50	=	7500.0	nM	PMID[28557430]
NPT1561	Protein complex	Cyclin-dependent kinase 1/cyclin B1	Homo sapiens	IC50	=	10000.0	nM	PMID[28557430]
NPT3944	Protein complex	Cyclin-dependent kinase 2/cyclin E1	Homo sapiens	IC50	=	2200.0	nM	PMID[28557430]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell line	A549	Homo sapiens	IC50	=	31000.0	nM	PMID[15993584]
NPT453	Cell line	HT-1080	Homo sapiens	IC50	=	42200.0	nM	PMID[15993584]
NPT116	Cell line	HL-60	Homo sapiens	IC50	>	100000.0	nM	PMID[15993584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	101.26	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	149.7	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	158.69	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	172.28	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	73.16	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	35.1	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	59.18	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	105.91	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	94.5	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	95.3	%	PMID[18024584]
NPT2891	Cell line	H4	Homo sapiens	Activity	=	100.5	%	PMID[18024584]
NPT1649	Cell line	MV4-11	Homo sapiens	IC50	>	10000.0	nM	PMID[20153646]
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	6100.0	nM	PMID[20627564]
NPT90	Cell line	DU-145	Homo sapiens	IC50	=	6800.0	nM	PMID[20627564]
NPT114	Cell line	LoVo	Homo sapiens	IC50	=	2200.0	nM	PMID[20627564]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	6700.0	nM	PMID[20627564]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	4000.0	nM	PMID[24326279]
NPT81	Cell line	A549	Homo sapiens	IC50	>	100000.0	nM	PMID[26883150]
NPT170	Cell line	SK-MEL-28	Homo sapiens	IC50	>	100000.0	nM	PMID[26883150]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	100000.0	nM	PMID[26883150]
NPT114	Cell line	LoVo	Homo sapiens	IC50	>	100000.0	nM	PMID[26883150]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	9910.0	nM	PMID[28557430]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	100000.0	nM	PMID[28743492]
NPT111	Cell line	K562	Homo sapiens	IC50	>	100000.0	nM	PMID[29678463]
NPT165	Cell line	HeLa	Homo sapiens	IC50	>	10000.0	nM	PMID[34624191]
NPT306	Cell line	PC-3	Homo sapiens	Activity	=	91.3	%	PMID[34161865]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	10000.0	nM	PMID[34624191]
NPT1045	Cell line	U2OS	Homo sapiens	Activity	=	40.0	%	PMID[34161865]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	10000.0	nM	PMID[34624191]
NPT81	Cell line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[34624191]
NPT1535	Cell line	U-87 MG	Homo sapiens	IC50	=	12500.0	nM	PMID[34161865]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	40000.0	nM	PMID[34161865]
NPT1045	Cell line	U2OS	Homo sapiens	Activity	=	38.0	%	PMID[34161865]
NPT111	Cell line	K562	Homo sapiens	IC50	>	10000.0	nM	PMID[34624191]
NPT306	Cell line	PC-3	Homo sapiens	Activity	=	77.1	%	PMID[34161865]
NPT2363	Cell line	U-118-MG	Homo sapiens	IC50	=	12500.0	nM	PMID[34161865]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	40000.0	nM	PMID[36170798]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	1100.0	nM	PMID[20627564]
NPT23408	Cell line	K562/VCR	Homo sapiens	IC50	>	100000.0	nM	PMID[29678463]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	2.15	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.12	%	DOI[10.6019/CHEMBL4495565]
NPT29120	Protein complex	CDK6/cyclin D3	Homo sapiens	Inhibition	=	25.1	%	PMID[34624191]
NPT28438	Unchecked	Unchecked	n.a.	IC50	=	7500.0	nM	PMID[34161865]
NPT28438	Unchecked	Unchecked	n.a.	IC50	=	10000.0	nM	PMID[35485642]
NPT28438	Unchecked	Unchecked	n.a.	IC50	=	10000.0	nM	PMID[34161865]
NPT610	Others	Molecular identity unknown	n.a.	FC	=	2.04	n.a.	PMID[19282173]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[20153646]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	10000.0	nM	PMID[20488718]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	6900.0	nM	PMID[20627564]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	9900.0	nM	PMID[24326279]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	100000.0	nM	PMID[26883150]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	30500.0	nM	PMID[26883150]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	200.0	nM	PMID[26883150]
NPT30138	Protein family	Histone deacetylase	Homo sapiens	Inhibition	=	17.2	%	PMID[34624191]
NPT22078	Protein family	Glycogen synthase kinase-3	Sus scrofa	IC50	=	1000.0	nM	PMID[34161865]
NPT30024	Protein complex	Cyclin-dependent kinase 5/CDK5 activator 1	Homo sapiens	IC50	=	5500.0	nM	PMID[34161865]
NPT29662	Protein complex	Cyclin-dependent kinase 4/cyclin D1	Homo sapiens	IC50	=	12000.0	nM	PMID[35485642]
NPT28597	Protein complex	CDK2/Cyclin A2	Homo sapiens	Inhibition	=	8.5	%	PMID[34624191]
NPT30024	Protein complex	Cyclin-dependent kinase 5/CDK5 activator 1	Homo sapiens	IC50	=	10000.0	nM	PMID[34161865]
NPT28597	Protein complex	CDK2/Cyclin A2	Homo sapiens	IC50	=	2200.0	nM	PMID[35485642]
NPT28597	Protein complex	CDK2/Cyclin A2	Homo sapiens	IC50	=	2200.0	nM	PMID[34161865]
NPT29662	Protein complex	Cyclin-dependent kinase 4/cyclin D1	Homo sapiens	IC50	=	12000.0	nM	PMID[34161865]
NPT28347	Protein complex	CDK4/Cyclin D3	Homo sapiens	Inhibition	=	1.0	%	PMID[34624191]
NPT24246	Protein family	Cyclin-dependent kinase	Homo sapiens	IC50	=	2200.0	nM	PMID[28722414]
NPT2	Others	Unspecified	n.a.	IC50	=	20000.0	nM	PMID[12672248]
NPT2	Others	Unspecified	n.a.	IC50	>	100000.0	nM	PMID[26883150]
NPT2	Others	Unspecified	n.a.	IC50	=	10000.0	nM	PMID[20488718]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	501.2	nM	PubChem BioAssay data set
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	>	32000.0	nM	PMID[24314672]
NPT22036	Cell line	HL	Homo sapiens	Activity	=	92.5	%	PMID[29043803]
NPT486	Organism	Toxoplasma gondii	Toxoplasma gondii	ID50	>	500.0	uM	PMID[18824607]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT519	Cell line	SH-SY5Y	Homo sapiens	Survival	=	104.0	%	PMID[16854069]
NPT617	Organism	Danio rerio	Danio rerio	IC50	<	100.0	nM	PubChem BioAssay data set

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC300596 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	36232
0.1-0.2	13384
0.2-0.3	222
0.3-0.4	17
0.4-0.5	2
0.5-0.6	1
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.5781	Remote Similarity	NPC482688

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC300596 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4409
0.1-0.2	4623
0.2-0.3	115
0.3-0.4	3
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data