NPASS Compound

Natural Product: NPC32867

Natural Product ID	NPC32867
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Volkensiflavone
IUPAC Name	8-[(2R,3S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-2,3-dihydrochromen-3-yl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
Synonyms	(+)-Volkensiflavone; (+/-)-Volkensiflavone; Volkensiflavone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL463023
PubChem CID	23844069
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 60 65 0 0 0 0 0 0 0 0999 V2000 4.2705 0.4345 -2.1729 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4887 1.1265 -3.3799 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4289 1.5925 -4.1202 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1453 1.3749 -3.6679 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9438 0.6955 -2.4837 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0014 0.2144 -1.7170 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7104 -0.4934 -0.4778 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7119 -0.9883 0.3216 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4636 -1.6725 1.5180 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3628 -2.1197 2.2408 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1419 -1.8270 1.8587 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7962 -2.4853 3.0186 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4668 -2.6248 3.3363 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4933 -2.1082 2.4961 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1761 -1.4448 1.3288 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2156 -0.8930 0.4524 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0675 -1.2153 -0.9790 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2742 -2.0832 -1.4356 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8828 -0.4950 -1.9392 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8585 -0.8759 -3.2814 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6397 -0.1791 -4.1747 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4299 0.8731 -3.7539 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4362 1.2314 -2.4167 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6698 0.5548 -1.5132 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6385 0.8751 -0.1494 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4622 0.5616 0.6172 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7237 1.0076 1.9862 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7597 1.7002 2.6892 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9842 2.1366 3.9934 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1766 1.8903 4.6225 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1479 1.1995 3.9316 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9206 0.7708 2.6435 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4017 2.3299 5.9352 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2145 1.5673 -4.6730 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0525 -1.9361 -3.6605 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1635 -1.3065 1.0134 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4470 -0.6774 -0.0895 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8203 -2.2758 2.8619 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8113 -2.9781 3.8141 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5825 2.2804 -5.3163 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1216 0.0894 -1.6287 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4857 1.2993 -3.7378 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3071 1.7421 -4.2511 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9350 0.5285 -2.1347 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7507 -0.8665 0.0532 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2092 -3.1401 4.2438 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1945 -1.3979 0.7501 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6411 -0.4505 -5.2161 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0409 2.0464 -2.0573 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5847 1.1095 0.2168 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2150 1.9308 2.2466 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2237 2.6840 4.5504 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0830 1.0124 4.4400 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6830 0.2228 2.0864 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7749 2.9583 6.3868 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1555 1.2371 -4.8867 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2749 -2.8975 -3.4380 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1098 -1.9614 3.7754 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8933 -2.7962 4.8037 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3582 2.9124 -5.4803 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 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 30 33 1 0 22 34 1 0 20 35 1 0 15 36 2 0 36 37 1 0 14 38 1 0 12 39 1 0 3 40 1 0 6 1 1 0 37 7 1 0 36 11 1 0 26 16 1 0 32 27 1 0 24 19 1 0 1 41 1 0 2 42 1 0 4 43 1 0 5 44 1 0 8 45 1 0 13 46 1 0 16 47 1 1 21 48 1 0 23 49 1 0 26 50 1 6 28 51 1 0 29 52 1 0 31 53 1 0 32 54 1 0 33 55 1 0 34 56 1 0 35 57 1 0 38 58 1 0 39 59 1 0 40 60 1 0 M END

Standard InCHIKey	YOGANETYFUQWIM-PXJZQJOASA-N
Standard InCHI	InChI=1S/C30H20O10/c31-15-5-1-13(2-6-15)22-12-21(37)24-19(35)11-20(36)26(30(24)39-22)27-28(38)25-18(34)9-17(33)10-23(25)40-29(27)14-3-7-16(32)8-4-14/h1-12,27,29,31-36H/t27-,29+/m1/s1
SMILES	c1cc(ccc1c1cc(=O)c2c(cc(c([C@@H]3C(=O)c4c(cc(cc4O[C@H]3c3ccc(cc3)O)O)O)c2o1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	540.11	Volume:	524.453 ? Van der Waals volume.
Dense:	1.03	LogP:	4.236 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.21 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.751 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	177.89 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.186	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.767	Fsp³:	0.067
MCE-18:	112.5 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.987	Fluc inhibitor:	0.738 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.662 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.949 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.585	Promiscuous compounds:	0.596

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.574	MDCK Permeability:	-4.844
Pgp-inhibitor:	0.099	Pgp-substrate:	0.312
PAMPA:	0.51 ? 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):	0.0
20% Bioavailability (F20%):	0.07	30% Bioavailability (F30%):	0.992
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.822
Plasma Protein Binding (PPB):	96.114%	Volume Distribution (VD):	-0.344
Fu:	5.504% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.996
BSEP inhibitor:	0.854

ADMET: Metabolism

CYP1A2-inhibitor:	0.007	CYP1A2-substrate:	0.029
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.072
CYP2C9-inhibitor:	0.949	CYP2C9-substrate:	0.028
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.128
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.827 ? 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):

2.81

Half-life (T1/2):

2.383

ADMET: Toxicity

hERG Blockers:	0.104	hERG Blockers (10um):	0.523
Human Hepatotoxicity (H-HT):	0.842	Drug-induced Liver Injury (DILI):	0.709
AMES Toxicity:	0.518	Rat Oral Acute Toxicity:	0.578
Maximum Recommended Daily Dose:	0.967	Skin Sensitization:	0.91
Carcinogencity:	0.325	Eye Corrosion:	0.0
Eye Irritation:	0.986	Respiratory Toxicity:	0.909
Drug-induced Neurotoxicity:	0.074	Ototoxicity:	0.264
Hematotoxicity:	0.024	Drug-induced Nephrotoxicity:	0.073
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.117
A549 Cytotoxicity:	0.787	Hek293 Cytotoxicity:	0.99
BCF:	1.14 ? 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:	4.178 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.637 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.316 ? 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
NPO5638	Garcinia livingstonei	Species	Clusiaceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1016/S0040-4020(01)89039-6]
NPO32446	calophyllum panciflorum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10654415]
NPO5049	Garcinia multiflora	Species	Clusiaceae	Eukaryota	stems	n.a.	n.a.	PMID[12932126]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	xylem	n.a.	PMID[14600386]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	fruits	n.a.	n.a.	PMID[15787435]
NPO5638	Garcinia livingstonei	Species	Clusiaceae	Eukaryota	root bark	n.a.	n.a.	PMID[16562837]
NPO5049	Garcinia multiflora	Species	Clusiaceae	Eukaryota	twigs	n.a.	n.a.	PMID[20681570]
NPO30436	Rheedia edulis	Species	Clusiaceae	Eukaryota	seeds and rinds	n.a.	n.a.	PMID[21028890]
NPO30436	Rheedia edulis	Species	Clusiaceae	Eukaryota	n.a.	exocarp	n.a.	PMID[21028890]
NPO30436	Rheedia edulis	Species	Clusiaceae	Eukaryota	n.a.	seed	n.a.	PMID[21028890]
NPO5638	Garcinia livingstonei	Species	Clusiaceae	Eukaryota	n.a.	fruit	n.a.	PMID[21028890]
NPO5049	Garcinia multiflora	Species	Clusiaceae	Eukaryota	Twigs and leaves	Taichung, Taiwan	1993-Aug	PMID[9322359]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5049	Garcinia multiflora	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5638	Garcinia livingstonei	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22337	Garcinia dulcis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5049	Garcinia multiflora	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22337	Garcinia dulcis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22337	Garcinia dulcis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5049	Garcinia multiflora	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5049	Garcinia multiflora	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5638	Garcinia livingstonei	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22337	Garcinia dulcis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5049	Garcinia multiflora	Species	Clusiaceae	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
Inhibition	2
Activity	7
IC50	7

Activity Type	# Activity
Individual protein	2
Cell line	6
Others	1
Organism	4
Non-molecular	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT459	Individual protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	Inhibition	=	30.0	%	PMID[9322359]
NPT459	Individual protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	Inhibition	=	45.3	%	PMID[9322359]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT80	Cell line	Raji	Homo sapiens	Activity	=	70.0	%	PMID[10654415]
NPT80	Cell line	Raji	Homo sapiens	Activity	>	80.0	%	PMID[10654415]
NPT660	Cell line	SW480	Homo sapiens	IC50	=	185000.0	nM	PMID[15787435]
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	40000.0	nM	PMID[16562837]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	48000.0	nM	PMID[16562837]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	40.1	%	PMID[10654415]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	72.6	%	PMID[10654415]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	91.2	%	PMID[10654415]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	56000.0	nM	PMID[16562837]
NPT1021	Organism	Leishmania infantum	Leishmania infantum	IC50	>	64000.0	nM	PMID[16562837]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	298000.0	nM	PMID[15787435]
NPT471	Organism	Trypanosoma brucei brucei	Trypanosoma brucei brucei	IC50	=	37000.0	nM	PMID[16562837]

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 NPC32867 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	24588
0.1-0.2	21072
0.2-0.3	3567
0.3-0.4	572
0.4-0.5	50
0.5-0.6	4
0.6-0.7	1
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9167	High Similarity	NPC320741
0.9167	High Similarity	NPC171985
0.8026	Intermediate Similarity	NPC295090
0.7692	Intermediate Similarity	NPC107627
0.6162	Remote Similarity	NPC132111
0.5652	Remote Similarity	NPC66441
0.5368	Remote Similarity	NPC182555
0.5165	Remote Similarity	NPC604941
0.5055	Remote Similarity	NPC607079

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC32867 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4077
0.1-0.2	4995
0.2-0.3	63
0.3-0.4	13
0.4-0.5	2
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