NPASS Compound

Natural Product: NPC12200

Natural Product ID	NPC12200
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(3,4-Dimethoxyphenyl)-5,7-Dihydroxychromen-4-One
IUPAC Name	2-(3,4-dimethoxyphenyl)-5,7-dihydroxychromen-4-one
Synonyms	NSC-128305
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL76426
PubChem CID	5351234
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002596] 4'-O-methylated flavonoids

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 37 39 0 0 0 0 0 0 0 0999 V2000 -5.2490 2.1672 1.3650 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8956 1.0037 0.6611 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5699 0.7229 0.4422 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5651 1.5801 0.9106 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2448 1.2699 0.6744 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9067 0.1056 -0.0293 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9230 -0.7081 -0.4716 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2589 -0.4241 -0.2503 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2320 -1.2863 -0.7230 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9787 -2.4582 -1.4280 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5089 -0.1566 -0.2409 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8928 -1.2816 -0.9232 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2430 -1.5486 -1.1350 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5727 -2.5791 -1.7592 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1607 -0.6561 -0.6420 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5204 -0.8678 -0.8214 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4440 0.0293 -0.3260 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0196 1.1517 0.3564 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6650 1.3486 0.5268 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7207 0.4680 0.0420 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4391 0.6524 0.2021 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9388 2.0844 0.8732 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8946 -2.0204 -1.5197 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6747 2.2949 2.2956 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3181 2.0710 1.6674 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1026 3.0911 0.7478 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8198 2.4895 1.4600 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4271 1.9020 1.0169 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7024 -1.6060 -1.0128 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1489 -3.0514 -1.0233 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7839 -2.3058 -2.5099 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9008 -3.1021 -1.3413 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2005 -2.0201 -1.3338 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5017 -0.1438 -0.4705 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3579 2.2391 1.0671 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6520 2.4368 0.2330 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9696 -2.8919 -1.0315 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 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 1 0 6 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 18 22 1 0 16 23 1 0 8 3 1 0 21 11 1 0 20 15 1 0 1 24 1 0 1 25 1 0 1 26 1 0 4 27 1 0 5 28 1 0 7 29 1 0 10 30 1 0 10 31 1 0 10 32 1 0 12 33 1 0 17 34 1 0 19 35 1 0 22 36 1 0 23 37 1 0 M END

Standard InCHIKey	AOLOMULCAJQEIG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H14O6/c1-21-13-4-3-9(5-15(13)22-2)14-8-12(20)17-11(19)6-10(18)7-16(17)23-14/h3-8,18-19H,1-2H3
SMILES	COc1ccc(cc1OC)c1cc(=O)c2c(cc(cc2o1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	314.08	Volume:	308.569 ? Van der Waals volume.
Dense:	1.018	LogP:	2.795 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.496 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.984 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	89.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.772	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.213	Fsp³:	0.118
MCE-18:	18.0 ? 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:	0.354	Fluc inhibitor:	0.928 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.944 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.733 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.398	Promiscuous compounds:	0.81

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.035	MDCK Permeability:	-4.794
Pgp-inhibitor:	0.23	Pgp-substrate:	0.578
PAMPA:	0.046 ? 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):	0.045
20% Bioavailability (F20%):	0.274	30% Bioavailability (F30%):	0.759
50% Bioavailability (F50%):	0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.662
Plasma Protein Binding (PPB):	97.638%	Volume Distribution (VD):	-0.196
Fu:	2.162% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.857
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.995
BSEP inhibitor:	0.94

ADMET: Metabolism

CYP1A2-inhibitor:	0.968	CYP1A2-substrate:	0.102
CYP2C19-inhibitor:	0.013	CYP2C19-substrate:	0.03
CYP2C9-inhibitor:	0.451	CYP2C9-substrate:	0.894
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.987
CYP3A4-inhibitor:	0.063	CYP3A4-substrate:	0.386
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.985
HLM stability:	0.709 ? 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):

5.108

Half-life (T1/2):

1.339

ADMET: Toxicity

hERG Blockers:	0.092	hERG Blockers (10um):	0.507
Human Hepatotoxicity (H-HT):	0.423	Drug-induced Liver Injury (DILI):	0.766
AMES Toxicity:	0.628	Rat Oral Acute Toxicity:	0.473
Maximum Recommended Daily Dose:	0.777	Skin Sensitization:	0.559
Carcinogencity:	0.8	Eye Corrosion:	0.692
Eye Irritation:	0.997	Respiratory Toxicity:	0.824
Drug-induced Neurotoxicity:	0.093	Ototoxicity:	0.08
Hematotoxicity:	0.113	Drug-induced Nephrotoxicity:	0.045
Genotoxicity:	0.886	RPMI-8226 Immunitoxicity:	0.068
A549 Cytotoxicity:	0.216	Hek293 Cytotoxicity:	0.657
BCF:	0.971 ? 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:	3.701 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.368 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.894 ? 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
NPO40877	Malagasy connaraceous	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[14510616]
NPO40069	Chresta martii	Species	Asteraceae	Eukaryota	Aerial Parts	n.a.	n.a.	PMID[30067035]
NPO40069	Chresta martii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Inhibition	3
IC50	7
GI50	59
Activity	2

Activity Type	# Activity
Individual protein	3
Cell line	62
Organism	2
Others	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1604	Individual protein	Cytochrome P450 1B1	Homo sapiens	IC50	=	19.0	nM	PMID[28458135]
NPT2266	Individual protein	Fructose-1,6-bisphosphatase	Homo sapiens	Inhibition	<	20.0	%	PMID[32364726]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Inhibition	<	50.0	%	PMID[24368208]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT517	Cell line	Panel NCI-60 (60 carcinoma cell lines)	Homo sapiens	GI50	=	48000.0	nM	PMID[9632366]
NPT521	Cell line	RBL-2H3	Rattus norvegicus	IC50	>	500000.0	nM	PMID[14510616]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	59566.21	nM	PubChem BioAssay data set
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	35481.34	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	36728.23	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	39902.49	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	2296.15	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	18407.72	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	57016.43	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	22961.49	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	92682.98	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	4570.88	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	46025.66	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	23988.33	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	43954.16	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	56754.46	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	29991.63	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	26607.25	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	9204.5	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	16749.43	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	33036.95	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	64863.44	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	17864.88	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	61801.64	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	4688.13	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	28444.61	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	28183.83	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	83752.93	nM	PubChem BioAssay data set
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	55080.77	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	47424.2	nM	PubChem BioAssay data set
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	71944.9	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	44668.36	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	61376.2	nM	PubChem BioAssay data set
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	44771.33	nM	PubChem BioAssay data set
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	11508.0	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	92044.96	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	68865.23	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	41783.04	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	81846.48	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	46344.69	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	17000.0	nM	PMID[27955927]
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	5000.0	nM	PMID[27955927]
NPT2	Others	Unspecified	n.a.	IC50	=	3330.0	nM	PMID[23871908]
NPT2	Others	Unspecified	n.a.	Inhibition	<	40.0	%	PMID[23871908]
NPT2	Others	Unspecified	n.a.	IC50	=	16000.0	nM	PMID[23871908]
NPT2	Others	Unspecified	n.a.	IC50	=	57600.0	nM	PMID[23871908]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	109.0	%	PMID[27955927]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	112.0	%	PMID[27955927]

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 NPC12200 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	28412
0.1-0.2	18024
0.2-0.3	2161
0.3-0.4	871
0.4-0.5	247
0.5-0.6	91
0.6-0.7	31
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8036	Intermediate Similarity	NPC605634
0.7925	Intermediate Similarity	NPC231772
0.7925	Intermediate Similarity	NPC62536
0.7667	Intermediate Similarity	NPC183
0.75	Intermediate Similarity	NPC52005
0.75	Intermediate Similarity	NPC606638
0.7368	Intermediate Similarity	NPC183950
0.7321	Intermediate Similarity	NPC159103
0.7321	Intermediate Similarity	NPC255350
0.7273	Intermediate Similarity	NPC120464
0.7273	Intermediate Similarity	NPC483773
0.7193	Intermediate Similarity	NPC195202
0.7193	Intermediate Similarity	NPC603596
0.6964	Remote Similarity	NPC601901
0.6897	Remote Similarity	NPC604422
0.6842	Remote Similarity	NPC600900
0.6761	Remote Similarity	NPC88023
0.6761	Remote Similarity	NPC309025
0.6724	Remote Similarity	NPC69394
0.661	Remote Similarity	NPC283600
0.6528	Remote Similarity	NPC165970
0.6481	Remote Similarity	NPC50898
0.6481	Remote Similarity	NPC78540
0.6438	Remote Similarity	NPC288131
0.6333	Remote Similarity	NPC2476
0.6324	Remote Similarity	NPC303485
0.6271	Remote Similarity	NPC163780
0.625	Remote Similarity	NPC112954
0.625	Remote Similarity	NPC279121
0.6232	Remote Similarity	NPC272064
0.6184	Remote Similarity	NPC113163
0.6176	Remote Similarity	NPC150908
0.6167	Remote Similarity	NPC183597
0.6104	Remote Similarity	NPC66618
0.6104	Remote Similarity	NPC305987
0.6102	Remote Similarity	NPC241838
0.6087	Remote Similarity	NPC71061
0.6087	Remote Similarity	NPC72425
0.6071	Remote Similarity	NPC175013
0.6061	Remote Similarity	NPC213622
0.6056	Remote Similarity	NPC601565
0.6	Remote Similarity	NPC63454
0.6	Remote Similarity	NPC183851
0.6	Remote Similarity	NPC186227
0.5942	Remote Similarity	NPC600972
0.5932	Remote Similarity	NPC219330
0.5915	Remote Similarity	NPC215203
0.5902	Remote Similarity	NPC54394
0.5862	Remote Similarity	NPC333230
0.5857	Remote Similarity	NPC290830
0.5833	Remote Similarity	NPC59951
0.5833	Remote Similarity	NPC610359
0.5806	Remote Similarity	NPC162351
0.5806	Remote Similarity	NPC200316
0.5806	Remote Similarity	NPC609179
0.5797	Remote Similarity	NPC134796
0.5763	Remote Similarity	NPC23955
0.569	Remote Similarity	NPC274121
0.5667	Remote Similarity	NPC77955
0.5667	Remote Similarity	NPC113089
0.5667	Remote Similarity	NPC215932
0.5667	Remote Similarity	NPC156222
0.5667	Remote Similarity	NPC29353
0.5645	Remote Similarity	NPC82325
0.5593	Remote Similarity	NPC213216
0.5588	Remote Similarity	NPC34089
0.5588	Remote Similarity	NPC196179
0.5574	Remote Similarity	NPC33265
0.5574	Remote Similarity	NPC184136
0.5574	Remote Similarity	NPC70853
0.5574	Remote Similarity	NPC28274
0.5556	Remote Similarity	NPC256612
0.5538	Remote Similarity	NPC485299
0.5526	Remote Similarity	NPC101731
0.5513	Remote Similarity	NPC4390
0.55	Remote Similarity	NPC610974
0.5484	Remote Similarity	NPC256283
0.5484	Remote Similarity	NPC603662
0.5479	Remote Similarity	NPC143851
0.5469	Remote Similarity	NPC133953
0.5469	Remote Similarity	NPC125062
0.5455	Remote Similarity	NPC172202
0.5455	Remote Similarity	NPC284127
0.541	Remote Similarity	NPC241498
0.541	Remote Similarity	NPC184536
0.541	Remote Similarity	NPC103342
0.541	Remote Similarity	NPC600177
0.541	Remote Similarity	NPC605617
0.5397	Remote Similarity	NPC115798
0.5397	Remote Similarity	NPC50728
0.5397	Remote Similarity	NPC83508
0.5397	Remote Similarity	NPC166753
0.5373	Remote Similarity	NPC138299
0.5373	Remote Similarity	NPC111112
0.5352	Remote Similarity	NPC604322
0.5325	Remote Similarity	NPC243930
0.5323	Remote Similarity	NPC286342
0.5323	Remote Similarity	NPC50403
0.5323	Remote Similarity	NPC234133
0.5323	Remote Similarity	NPC145379
0.5323	Remote Similarity	NPC266597
0.5312	Remote Similarity	NPC177298
0.5312	Remote Similarity	NPC223579
0.5294	Remote Similarity	NPC301217
0.5294	Remote Similarity	NPC291746
0.525	Remote Similarity	NPC84324
0.5246	Remote Similarity	NPC293183
0.5246	Remote Similarity	NPC75279
0.5246	Remote Similarity	NPC85233
0.5231	Remote Similarity	NPC279989
0.5231	Remote Similarity	NPC137062
0.5217	Remote Similarity	NPC475212
0.5195	Remote Similarity	NPC191306
0.5161	Remote Similarity	NPC110639
0.5161	Remote Similarity	NPC301323
0.5161	Remote Similarity	NPC284552
0.5161	Remote Similarity	NPC123886
0.5161	Remote Similarity	NPC205522
0.5161	Remote Similarity	NPC127447
0.5152	Remote Similarity	NPC483775
0.5128	Remote Similarity	NPC601710
0.5079	Remote Similarity	NPC100887
0.5079	Remote Similarity	NPC48479
0.5079	Remote Similarity	NPC57030
0.5079	Remote Similarity	NPC120163
0.5077	Remote Similarity	NPC224137
0.5077	Remote Similarity	NPC160951
0.5077	Remote Similarity	NPC287101
0.5077	Remote Similarity	NPC236769
0.5077	Remote Similarity	NPC115323
0.5077	Remote Similarity	NPC607642
0.507	Remote Similarity	NPC224714
0.5067	Remote Similarity	NPC121649
0.5063	Remote Similarity	NPC607707
0.506	Remote Similarity	NPC476410

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC12200 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5220
0.1-0.2	3837
0.2-0.3	81
0.3-0.4	7
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
0.7-0.8	1
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
0.7321	Intermediate Similarity	NPD2801	Pre-clinical
0.625	Remote Similarity	NPD1511	Phase 2

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