NPASS Compound

Natural Product: NPC304495

Natural Product ID	NPC304495
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	22,23-Dihydrocucurbitacin E
IUPAC Name	[(6R)-6-[(8S,9R,10R,13R,14S,16R,17R)-2,16-dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-8,10,12,15,16,17-hexahydro-7H-cyclopenta[a]phenanthren-17-yl]-6-hydroxy-2-methyl-5-oxoheptan-2-yl] acetate
Synonyms	22,23-Dihydrocucurbitacin E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL256519
PubChem CID	21577087
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001686] Cucurbitacins

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 86 89 0 0 0 0 0 0 0 0999 V2000 9.5547 1.9117 -0.0483 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5111 0.9403 -0.4850 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8857 -0.1079 -1.0428 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1713 1.1518 -0.3001 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1466 0.2214 -0.7024 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2303 -0.0745 -2.1810 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4019 -1.0203 0.0803 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8685 0.9387 -0.4214 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5864 0.3155 -0.7588 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2366 -0.9306 -0.1141 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7819 -1.9589 -0.4107 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1607 -1.0165 0.9723 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5053 -0.0394 2.0108 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8896 -0.7714 0.1982 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7010 -1.8198 -0.8594 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7967 -2.1523 -0.9229 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3804 -0.9520 -0.2667 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2584 0.1217 -1.2787 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8197 -1.0900 0.1609 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6255 -1.3075 -1.0924 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5119 -0.2393 -1.5407 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9394 0.6766 -0.7617 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5388 0.6815 0.6393 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.7790 0.2441 1.3384 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9775 0.6840 0.8754 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0791 1.5662 -0.2784 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1440 2.1625 -0.5961 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8897 1.7752 -1.1149 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2889 3.1139 -0.7172 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1685 1.8379 -2.5848 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1648 0.3062 1.4899 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3242 -0.0276 1.0615 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6120 -0.4597 2.4800 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1480 0.9278 1.2247 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3100 2.1152 0.9962 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8504 0.3661 1.6574 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4093 -0.8392 0.9082 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4077 -2.1123 1.6970 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2757 -1.5735 -2.0682 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2856 -2.3065 1.4321 O 0 0 0 0 0 0 0 0 0 0 0 0 9.9006 1.5668 0.9456 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2009 2.9368 0.0442 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4535 1.8350 -0.7244 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3197 -0.6771 -2.4273 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0853 -0.7706 -2.4217 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1971 0.8094 -2.8200 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8109 -1.1006 1.0253 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4687 -0.9594 0.4856 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4335 -1.9576 -0.5127 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9680 1.9346 -0.9727 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9314 1.2334 0.6782 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7751 1.1087 -0.6508 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5254 0.1123 -1.8822 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0564 -0.2245 3.0085 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2890 1.0198 1.7651 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6208 -0.0772 2.1832 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0194 0.2620 -0.1683 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1732 -2.7703 -0.4665 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0544 -3.1143 -0.5177 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0253 -2.2006 -2.0304 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2041 0.5313 -1.6536 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5609 -0.1952 -2.0809 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6984 1.0364 -0.9113 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8465 -2.0790 0.7290 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1932 -2.2765 -0.9504 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9250 -1.4627 -1.9907 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8105 -0.2551 -2.6118 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4086 1.7555 0.9819 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8312 -0.3921 2.1768 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8269 3.9173 -1.2948 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2076 3.1597 -0.8527 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5479 3.3124 0.3514 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5348 0.8990 -3.0157 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8355 2.7121 -2.7569 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2066 2.1300 -3.0803 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2142 -0.6399 1.8431 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1750 -1.4183 2.5484 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1861 0.2785 3.0676 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6506 -0.5424 3.0811 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8203 0.2717 2.7655 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0925 1.1782 1.4275 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3969 -2.4433 2.0707 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2083 -2.0077 2.6440 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0105 -2.9753 1.1920 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3721 -2.4393 -2.5534 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6642 -2.2806 2.3491 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 5 7 1 0 5 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 6 17 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 28 30 1 0 25 31 1 0 23 32 1 0 32 33 1 1 32 34 1 0 34 35 2 0 34 36 1 0 36 37 1 0 37 38 1 1 15 39 1 0 12 40 1 1 37 14 1 0 37 17 1 0 32 19 1 0 28 22 1 0 1 41 1 0 1 42 1 0 1 43 1 0 6 44 1 0 6 45 1 0 6 46 1 0 7 47 1 0 7 48 1 0 7 49 1 0 8 50 1 0 8 51 1 0 9 52 1 0 9 53 1 0 13 54 1 0 13 55 1 0 13 56 1 0 14 57 1 6 15 58 1 1 16 59 1 0 16 60 1 0 18 61 1 0 18 62 1 0 18 63 1 0 19 64 1 1 20 65 1 0 20 66 1 0 21 67 1 0 23 68 1 1 24 69 1 0 29 70 1 0 29 71 1 0 29 72 1 0 30 73 1 0 30 74 1 0 30 75 1 0 31 76 1 0 33 77 1 0 33 78 1 0 33 79 1 0 36 80 1 0 36 81 1 0 38 82 1 0 38 83 1 0 38 84 1 0 39 85 1 0 40 86 1 0 M END

Standard InCHIKey	XZBVNQWNPRMHRH-LAMASETHSA-N
Standard InCHI	InChI=1S/C32H46O8/c1-17(33)40-27(2,3)13-12-23(36)32(9,39)25-21(35)15-29(6)22-11-10-18-19(14-20(34)26(38)28(18,4)5)31(22,8)24(37)16-30(25,29)7/h10,14,19,21-22,25,34-35,39H,11-13,15-16H2,1-9H3/t19-,21-,22+,25+,29+,30-,31+,32+/m1/s1
SMILES	CC(=O)OC(C)(C)CCC(=O)[C@@](C)([C@H]1[C@@H](C[C@@]2(C)[C@@H]3CC=C4[C@@H](C=C(C(=O)C4(C)C)O)[C@]3(C)C(=O)C[C@]12C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	558.32	Volume:	582.305 ? Van der Waals volume.
Dense:	0.959	LogP:	1.96 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.283 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.94 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	24.0
TPSA:	138.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.322	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.324	Fsp³:	0.75
MCE-18:	95.714 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.552	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.173 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.229	Promiscuous compounds:	0.346

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.947	MDCK Permeability:	-4.526
Pgp-inhibitor:	0.163	Pgp-substrate:	0.015
PAMPA:	0.991 ? 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):	0.031
20% Bioavailability (F20%):	0.471	30% Bioavailability (F30%):	0.918
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013	MRP1:	0.995
Plasma Protein Binding (PPB):	83.692%	Volume Distribution (VD):	-0.019
Fu:	19.299% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.265
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.082	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.503	CYP2C19-substrate:	0.663
CYP2C9-inhibitor:	0.045	CYP2C9-substrate:	0.005
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.961 ? 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):

4.948

Half-life (T1/2):

1.11

ADMET: Toxicity

hERG Blockers:	0.009	hERG Blockers (10um):	0.079
Human Hepatotoxicity (H-HT):	0.332	Drug-induced Liver Injury (DILI):	0.701
AMES Toxicity:	0.397	Rat Oral Acute Toxicity:	0.667
Maximum Recommended Daily Dose:	0.794	Skin Sensitization:	0.984
Carcinogencity:	0.38	Eye Corrosion:	0.0
Eye Irritation:	0.181	Respiratory Toxicity:	0.851
Drug-induced Neurotoxicity:	0.095	Ototoxicity:	0.348
Hematotoxicity:	0.722	Drug-induced Nephrotoxicity:	0.912
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.404
A549 Cytotoxicity:	0.052	Hek293 Cytotoxicity:	0.236
BCF:	0.512 ? 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:	3.295 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.97 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.335 ? 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
NPO40156	Hemsleya endecaphylla	Species	Cucurbitaceae	Eukaryota	Tubers	n.a.	n.a.	PMID[18088099]
NPO27538	Hemsleya macrosperma	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27538	Hemsleya macrosperma	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO27538	Hemsleya macrosperma	Species	Cucurbitaceae	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
EC50	1
IC50	2
CC50	1
Ratio CC50/EC50	1

Activity Type	# Activity
Cell line	3
Organism	1
Others	1

Molecular-level activity

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

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	>	100000.0	nM	PMID[22472043]
NPT1452	Cell line	C8166	Homo sapiens	CC50	=	21.6	ug.mL-1	PMID[18088099]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	2.4	ug.mL-1	PMID[18088099]
NPT2	Others	Unspecified	n.a.	Ratio CC50/EC50	=	9.2	n.a.	PMID[18088099]

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 NPC304495 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	17918
0.1-0.2	29836
0.2-0.3	2029
0.3-0.4	38
0.4-0.5	22
0.5-0.6	5
0.6-0.7	4
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
0.7727	Intermediate Similarity	NPC474720
0.7222	Intermediate Similarity	NPC221144
0.7206	Intermediate Similarity	NPC58370
0.7206	Intermediate Similarity	NPC43285
0.7042	Intermediate Similarity	NPC470257
0.6986	Remote Similarity	NPC196528
0.6757	Remote Similarity	NPC280782
0.6714	Remote Similarity	NPC111323
0.6119	Remote Similarity	NPC147954
0.5862	Remote Similarity	NPC486351
0.5375	Remote Similarity	NPC486346
0.5217	Remote Similarity	NPC479418
0.5195	Remote Similarity	NPC49371
0.5195	Remote Similarity	NPC479419

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC304495 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6990
0.1-0.2	2092
0.2-0.3	68
0.3-0.4	0
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