NPASS Compound

Natural Product: NPC163883

Natural Product ID	NPC163883
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl 5-O-Caffeoyl-4-O-Sinapoylquinate
IUPAC Name	methyl (1R,3R,4S,5R)-3-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy-1,4-dihydroxy-5-[(E)-3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-enoyl]oxycyclohexane-1-carboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL475065
PubChem CID	11671431
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000129] Alcohols and polyols [CHEMONTID:0001292] Cyclic alcohols and derivatives [CHEMONTID:0002509] Cyclitols and derivatives [CHEMONTID:0002512] Quinic acids and derivatives

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 71 73 0 0 0 0 0 0 0 0999 V2000 -9.0219 2.8831 2.4411 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4230 2.0252 1.4143 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4571 1.2935 0.7258 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1246 1.4015 1.0411 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1381 0.6756 0.3610 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7466 0.8050 0.7043 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7641 0.1694 0.1150 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3606 0.3709 0.5423 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0893 1.1451 1.4700 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2969 -0.2517 -0.0260 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0060 -0.0686 0.3647 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9532 0.5030 -0.6327 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2262 -0.4191 -1.8032 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1521 -0.3353 -2.6853 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3708 -1.8489 -1.3981 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5573 -2.0479 0.0659 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6255 -1.3140 0.9553 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4670 -2.1627 1.2607 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8891 -1.6393 0.4043 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8115 -2.5053 0.9688 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4625 -3.6722 1.1841 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1587 -1.9912 1.2843 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4821 -0.7499 1.0347 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7559 -0.1215 1.2919 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8002 -0.8009 1.8648 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0387 -0.2007 2.1150 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2439 1.1091 1.7869 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1933 1.8028 1.2078 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9873 1.2176 0.9643 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3708 3.1368 0.8623 O 0 0 0 0 0 0 0 0 0 0 0 0 10.4563 1.7825 2.0059 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4407 -0.0074 -2.5402 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3311 0.3184 -3.7448 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6914 0.0387 -1.9767 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8584 0.4356 -2.6898 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5482 -0.1563 -0.6416 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9008 -0.2849 -0.9834 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8390 0.4376 -0.2999 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1887 0.3624 -0.5806 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2993 -1.1436 -2.0146 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2903 -1.8682 -2.6889 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8297 2.2692 3.3515 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8543 3.5993 2.6611 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1333 3.4753 2.2283 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7589 2.0451 1.8267 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4841 1.4959 1.5286 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9742 -0.5065 -0.6874 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0207 0.6700 1.2171 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9347 0.6419 -0.1271 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6810 1.5133 -0.9957 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3243 0.2986 -3.4196 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4956 -2.4795 -1.7091 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2242 -2.2812 -1.9556 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5001 -3.1368 0.3434 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1456 -1.0935 1.9184 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1784 -1.5955 1.6610 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8854 -2.6370 1.7230 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6937 -0.1329 0.5834 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6678 -1.8438 2.1364 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8179 -0.7663 2.5609 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1638 1.7534 0.5133 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3089 3.4177 0.5976 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4914 2.7691 2.2410 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1826 1.4555 -2.3954 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6765 0.4789 -3.7817 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6567 -0.3185 -2.5306 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8358 -0.7409 -1.2007 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6301 -0.5263 -0.5733 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7167 -2.5093 -1.9978 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7767 -2.4995 -3.4616 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5649 -1.1398 -3.1301 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 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 6 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 16 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 27 31 1 0 13 32 1 0 32 33 2 0 32 34 1 0 34 35 1 0 5 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 37 40 1 0 40 41 1 0 38 3 1 0 17 11 1 0 29 24 1 0 1 42 1 0 1 43 1 0 1 44 1 0 4 45 1 0 6 46 1 0 7 47 1 0 11 48 1 1 12 49 1 0 12 50 1 0 14 51 1 0 15 52 1 0 15 53 1 0 16 54 1 6 17 55 1 1 18 56 1 0 22 57 1 0 23 58 1 0 25 59 1 0 26 60 1 0 29 61 1 0 30 62 1 0 31 63 1 0 35 64 1 0 35 65 1 0 35 66 1 0 36 67 1 0 39 68 1 0 41 69 1 0 41 70 1 0 41 71 1 0 M END

Standard InCHIKey	QXOKQINPRTYYQK-PIHNLQSFSA-N
Standard InCHI	InChI=1S/C28H30O13/c1-37-19-11-16(12-20(38-2)25(19)33)6-9-24(32)41-22-14-28(36,27(35)39-3)13-21(26(22)34)40-23(31)8-5-15-4-7-17(29)18(30)10-15/h4-12,21-22,26,29-30,33-34,36H,13-14H2,1-3H3/b8-5+,9-6+/t21-,22-,26+,28-/m1/s1
SMILES	COc1cc(/C=C/C(=O)O[C@@H]2C[C@](O)(C[C@H]([C@@H]2O)OC(=O)/C=C/c2ccc(c(c2)O)O)C(=O)OC)cc(c1O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	574.17	Volume:	552.447 ? Van der Waals volume.
Dense:	1.039	LogP:	1.894 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.094 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.243 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	23.0
TPSA:	198.51 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.125	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.183	Fsp³:	0.321
MCE-18:	83.108 ? 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:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.84	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.091 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.62 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.243	Promiscuous compounds:	0.478

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.128	MDCK Permeability:	-5.285
Pgp-inhibitor:	0.492	Pgp-substrate:	0.778
PAMPA:	0.374 ? 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):	0.194
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.674
Plasma Protein Binding (PPB):	69.486%	Volume Distribution (VD):	0.436
Fu:	34.209% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.366
BSEP inhibitor:	0.842

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.022
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.289
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.634 ? 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):

5.74

Half-life (T1/2):

2.42

ADMET: Toxicity

hERG Blockers:	0.065	hERG Blockers (10um):	0.384
Human Hepatotoxicity (H-HT):	0.596	Drug-induced Liver Injury (DILI):	0.376
AMES Toxicity:	0.441	Rat Oral Acute Toxicity:	0.072
Maximum Recommended Daily Dose:	0.981	Skin Sensitization:	0.997
Carcinogencity:	0.306	Eye Corrosion:	0.0
Eye Irritation:	0.088	Respiratory Toxicity:	0.128
Drug-induced Neurotoxicity:	0.061	Ototoxicity:	0.721
Hematotoxicity:	0.03	Drug-induced Nephrotoxicity:	0.792
Genotoxicity:	0.777	RPMI-8226 Immunitoxicity:	0.083
A549 Cytotoxicity:	0.84	Hek293 Cytotoxicity:	0.491
BCF:	0.599 ? 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:	3.501 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.905 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.494 ? 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
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[16309325]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	n.a.	Seoul, Korea	2000-Jun	PMID[16643034]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	fruit	n.a.	n.a.	PMID[18505286]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	fruit	n.a.	n.a.	PMID[19650637]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	fruits	n.a.	n.a.	PMID[23305920]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32141747]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9518	Gardenia jasminoides	Species	Rubiaceae	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	3
Inhibition	1

Activity Type	# Activity
Individual protein	1
Others	1
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT12	Individual protein	Human immunodeficiency virus type 1 integrase	Human immunodeficiency virus 1	IC50	=	23.6	ug.mL-1	PMID[16643034]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2.2	ug.mL-1	PMID[16643034]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	54.7	%	PMID[16643034]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	8.5	ug.mL-1	PMID[16643034]

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 NPC163883 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	11313
0.1-0.2	32529
0.2-0.3	5243
0.3-0.4	632
0.4-0.5	105
0.5-0.6	21
0.6-0.7	5
0.7-0.8	0
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.871	High Similarity	NPC146277
0.8214	Intermediate Similarity	NPC258469
0.8214	Intermediate Similarity	NPC43158
0.8214	Intermediate Similarity	NPC610147
0.7353	Intermediate Similarity	NPC93498
0.6719	Remote Similarity	NPC295492
0.6719	Remote Similarity	NPC303683
0.6719	Remote Similarity	NPC274891
0.6486	Remote Similarity	NPC19380
0.6094	Remote Similarity	NPC26241
0.5882	Remote Similarity	NPC277315
0.5882	Remote Similarity	NPC472016
0.5882	Remote Similarity	NPC192831
0.5738	Remote Similarity	NPC224208
0.5738	Remote Similarity	NPC41661
0.5714	Remote Similarity	NPC205751
0.5593	Remote Similarity	NPC200014
0.5588	Remote Similarity	NPC233350
0.5588	Remote Similarity	NPC70680
0.5556	Remote Similarity	NPC44730
0.5441	Remote Similarity	NPC13818
0.5439	Remote Similarity	NPC58279
0.5395	Remote Similarity	NPC306343
0.5263	Remote Similarity	NPC322660
0.5238	Remote Similarity	NPC474275
0.5161	Remote Similarity	NPC233669
0.5143	Remote Similarity	NPC474875
0.5139	Remote Similarity	NPC471027
0.5088	Remote Similarity	NPC226250
0.5065	Remote Similarity	NPC270993
0.506	Remote Similarity	NPC145425

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC163883 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3722
0.1-0.2	5278
0.2-0.3	146
0.3-0.4	3
0.4-0.5	1
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