NPASS Compound

Natural Product: NPC183597

Natural Product ID	NPC183597
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-Dihydroxy-6,8-Dimethoxychromen-4-One
IUPAC Name	2-(3,4-dimethoxyphenyl)-5,7-dihydroxy-6,8-dimethoxychromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL504325
PubChem CID	171488
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002593] 8-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 45 47 0 0 0 0 0 0 0 0999 V2000 -4.6623 3.3817 0.4673 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0992 2.0208 0.3312 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1204 1.0392 0.1391 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7716 1.3746 0.0825 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8279 0.3885 -0.1076 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2876 -0.9066 -0.2339 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6235 -1.2270 -0.1764 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5839 -0.2537 0.0134 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9375 -0.5473 0.0755 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3103 -1.9059 -0.0650 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4147 0.6759 -0.1749 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1065 1.9247 -0.0587 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4871 2.1240 -0.1345 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9621 3.2830 -0.0261 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3082 1.0369 -0.3282 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7173 -0.1987 -0.4377 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4187 -0.3348 -0.3601 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5431 -1.3076 -0.6344 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9903 -2.5670 -0.7495 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7540 -3.4343 0.3234 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9136 -1.2005 -0.7208 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4872 0.0465 -0.6087 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6730 1.1549 -0.4128 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2136 2.4274 -0.2952 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8525 0.2015 -0.6888 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7236 0.1488 0.4186 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7174 -2.3245 -0.9178 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8922 3.4400 1.2853 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4952 4.0348 0.7458 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1663 3.7373 -0.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5071 2.4168 0.1918 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5587 -1.6845 -0.3828 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9641 -2.2647 -0.2796 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4020 -2.0476 -0.0369 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7971 -2.4721 0.7574 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8688 -2.2743 -1.0192 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5423 2.7665 0.0922 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7117 -3.6590 0.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2973 -4.3677 -0.1085 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9959 -3.0032 1.0006 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3556 2.8675 0.6179 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9703 1.1966 0.6986 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1730 -0.2762 1.2962 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6569 -0.4111 0.2101 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8039 -3.0199 -0.1681 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 5 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 16 18 1 0 18 19 1 0 19 20 1 0 18 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 22 25 1 0 25 26 1 0 21 27 1 0 8 3 1 0 17 11 1 0 23 15 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 6 32 1 0 7 33 1 0 10 34 1 0 10 35 1 0 10 36 1 0 12 37 1 0 20 38 1 0 20 39 1 0 20 40 1 0 24 41 1 0 26 42 1 0 26 43 1 0 26 44 1 0 27 45 1 0 M END

Standard InCHIKey	QCOSAYZZNVASNN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C19H18O8/c1-23-11-6-5-9(7-13(11)24-2)12-8-10(20)14-15(21)18(25-3)16(22)19(26-4)17(14)27-12/h5-8,21-22H,1-4H3
SMILES	COc1cc(ccc1OC)c1cc(=O)c2c(o1)c(OC)c(c(c2O)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	374.1	Volume:	360.741 ? Van der Waals volume.
Dense:	1.037	LogP:	2.272 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.33 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.082 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	18.0
TPSA:	107.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.702	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.495	Fsp³:	0.211
MCE-18:	20.0 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.209	Fluc inhibitor:	0.524 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.805 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.644 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.332	Promiscuous compounds:	0.825

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.193	MDCK Permeability:	-4.776
Pgp-inhibitor:	0.893	Pgp-substrate:	0.36
PAMPA:	0.031 ? 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):	0.038
20% Bioavailability (F20%):	0.077	30% Bioavailability (F30%):	0.24
50% Bioavailability (F50%):	0.877

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.041	MRP1:	0.904
Plasma Protein Binding (PPB):	96.62%	Volume Distribution (VD):	-0.48
Fu:	3.047% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.904
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.987
BSEP inhibitor:	0.971

ADMET: Metabolism

CYP1A2-inhibitor:	0.927	CYP1A2-substrate:	0.198
CYP2C19-inhibitor:	0.042	CYP2C19-substrate:	0.319
CYP2C9-inhibitor:	0.216	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.985	CYP2D6-substrate:	0.314
CYP3A4-inhibitor:	0.677	CYP3A4-substrate:	0.285
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.887
HLM stability:	0.766 ? 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):

3.888

Half-life (T1/2):

1.714

ADMET: Toxicity

hERG Blockers:	0.106	hERG Blockers (10um):	0.497
Human Hepatotoxicity (H-HT):	0.444	Drug-induced Liver Injury (DILI):	0.742
AMES Toxicity:	0.452	Rat Oral Acute Toxicity:	0.378
Maximum Recommended Daily Dose:	0.373	Skin Sensitization:	0.672
Carcinogencity:	0.701	Eye Corrosion:	0.525
Eye Irritation:	0.968	Respiratory Toxicity:	0.697
Drug-induced Neurotoxicity:	0.281	Ototoxicity:	0.193
Hematotoxicity:	0.356	Drug-induced Nephrotoxicity:	0.174
Genotoxicity:	0.231	RPMI-8226 Immunitoxicity:	0.083
A549 Cytotoxicity:	0.182	Hek293 Cytotoxicity:	0.335
BCF:	1.041 ? 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:	3.523 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.393 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.882 ? 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
NPO26558	Physocarpus capitatus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9277	Ammothamnus songoricus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26779	Helianthus strumosus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26779	Helianthus strumosus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26706	Dictyota pardalis	Species	Dictyotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12676	Berberis mingetsensis	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26558	Physocarpus capitatus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26852	Cryptocarya konishii	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26114	Dorstenia convexa	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9277	Ammothamnus songoricus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10843	Melanelixia subglabra	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4202	Kopsia terengganensis	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26779	Helianthus strumosus	Species	Asteraceae	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	1
GI50	51

Activity Type	# Activity
Cell line	51
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT68	Individual protein	Aldose reductase	Rattus norvegicus	IC50	=	29512.09	nM	PMID[18585047]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	43351.09	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	33036.95	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	21527.82	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	25061.09	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	41304.75	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	46238.1	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	100000.0	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.	45919.8	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	36391.5	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	42266.86	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	44157.04	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	49888.45	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT572	Cell line	DMS-273	Homo sapiens	GI50	n.a.	54075.43	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	31188.9	nM	PubChem BioAssay data set
NPT573	Cell line	M19-MEL	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.	11994.99	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT574	Cell line	XF498	Homo sapiens	GI50	n.a.	78342.96	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.	46025.66	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT575	Cell line	KM-20L2	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
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	72110.75	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	21827.3	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	63679.55	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	57016.43	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	90157.11	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT731	Cell line	LXFL 529	Homo sapiens	GI50	n.a.	61094.2	nM	PubChem BioAssay data set
NPT576	Cell line	DMS-114	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	79983.43	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	47424.2	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	84333.48	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT578	Cell line	SNB-78	Homo sapiens	GI50	n.a.	41975.9	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT579	Cell line	DLD-1	Homo sapiens	GI50	n.a.	54827.7	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	33573.76	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	22233.1	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.	14125.38	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	92257.14	nM	PubChem BioAssay data set
NPT732	Cell line	HOP-18	Homo sapiens	GI50	n.a.	54325.03	nM	PubChem BioAssay data set

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC183597 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	29329
0.1-0.2	17642
0.2-0.3	2234
0.3-0.4	457
0.4-0.5	139
0.5-0.6	37
0.6-0.7	8
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
0.7885	Intermediate Similarity	NPC274327
0.7455	Intermediate Similarity	NPC146165
0.7358	Intermediate Similarity	NPC602963
0.7321	Intermediate Similarity	NPC4455
0.7321	Intermediate Similarity	NPC2476
0.7222	Intermediate Similarity	NPC275836
0.7018	Intermediate Similarity	NPC256612
0.6842	Remote Similarity	NPC255350
0.6667	Remote Similarity	NPC163780
0.6552	Remote Similarity	NPC69394
0.6379	Remote Similarity	NPC600155
0.6167	Remote Similarity	NPC283600
0.6167	Remote Similarity	NPC195202
0.6167	Remote Similarity	NPC12200
0.6034	Remote Similarity	NPC110639
0.5862	Remote Similarity	NPC7973
0.5862	Remote Similarity	NPC250822
0.5862	Remote Similarity	NPC85233
0.5763	Remote Similarity	NPC205522
0.5763	Remote Similarity	NPC600177
0.5672	Remote Similarity	NPC213622
0.5667	Remote Similarity	NPC176775
0.5645	Remote Similarity	NPC78302
0.5645	Remote Similarity	NPC604422
0.5484	Remote Similarity	NPC204854
0.5424	Remote Similarity	NPC333230
0.541	Remote Similarity	NPC70853
0.5397	Remote Similarity	NPC196439
0.5333	Remote Similarity	NPC131624
0.5333	Remote Similarity	NPC23955
0.5312	Remote Similarity	NPC227325
0.5246	Remote Similarity	NPC191459
0.5246	Remote Similarity	NPC77955
0.5246	Remote Similarity	NPC301323
0.5246	Remote Similarity	NPC113089
0.5246	Remote Similarity	NPC215932
0.5246	Remote Similarity	NPC156222
0.5238	Remote Similarity	NPC115798
0.5238	Remote Similarity	NPC608498
0.5161	Remote Similarity	NPC145379
0.5161	Remote Similarity	NPC130894
0.5161	Remote Similarity	NPC231018
0.5161	Remote Similarity	NPC188203
0.5161	Remote Similarity	NPC604462
0.5156	Remote Similarity	NPC224137
0.5156	Remote Similarity	NPC288669
0.5156	Remote Similarity	NPC7846
0.5152	Remote Similarity	NPC485299
0.5082	Remote Similarity	NPC75279
0.5079	Remote Similarity	NPC201136
0.5079	Remote Similarity	NPC134677
0.5079	Remote Similarity	NPC256283

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC183597 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5154
0.1-0.2	3922
0.2-0.3	67
0.3-0.4	5
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
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
0.6842	Remote Similarity	NPD2801	Pre-clinical

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