NPASS Compound

Natural Product: NPC476729

Natural Product ID	NPC476729
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	methyl (1R,2S,3R,6R,8R,13S,14R,15R,16S,17R)-10,15,16-trihydroxy-3-[(E)-4-hydroxy-3,4-dimethylpent-2-enoyl]oxy-9,13-dimethyl-4,11-dioxo-5,18-dioxapentacyclo[12.5.0.01,6.02,17.08,13]nonadec-9-ene-17-carboxylate
IUPAC Name	methyl (1R,2S,3R,6R,8R,13S,14R,15R,16S,17R)-10,15,16-trihydroxy-3-[(E)-4-hydroxy-3,4-dimethylpent-2-enoyl]oxy-9,13-dimethyl-4,11-dioxo-5,18-dioxapentacyclo[12.5.0.01,6.02,17.08,13]nonadec-9-ene-17-carboxylate
Synonyms	Bruceine C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44584512
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0002119] Quassinoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 76 80 0 0 0 0 0 0 0 0999 V2000 -2.3313 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -5.2500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2668 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5658 -5.2500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8648 -6.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5658 -3.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2668 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -3.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3313 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3313 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2668 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2894 -0.7599 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3740 0.4929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3313 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6304 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9294 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6304 -0.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3671 2.6491 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8802 4.0586 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3574 4.3191 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9160 5.2077 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4290 6.6172 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9062 6.8777 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4648 7.7663 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6842 6.8021 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6139 8.7305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4993 8.9153 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5760 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1780 -0.5478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8578 2.6401 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1459 3.7548 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3250 2.9520 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7886 4.3786 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1200 0.0738 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0325 -2.5271 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5658 -2.2500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2668 -7.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5813 -7.2990 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3734 -4.9210 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6304 -6.7500 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0002 -4.1886 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7946 -2.8898 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3313 -4.5000 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8293 -2.9215 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1702 -4.2435 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7121 -2.0861 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4647 -0.5972 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0397 -0.7242 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2353 1.7873 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5192 2.1595 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2955 2.6491 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5820 5.1292 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8278 8.3756 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1667 5.4005 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3834 7.1382 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7813 7.8251 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0267 5.4539 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8333 5.8379 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6497 9.8795 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9259 8.0034 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7630 9.6946 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9973 8.8369 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7751 -1.7996 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1339 -2.6908 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2152 3.9150 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4291 5.0125 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2521 5.8051 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1371 1.1763 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4959 -2.8566 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7316 -3.1939 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0544 -0.8318 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9466 -1.6639 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5658 -8.2500 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 17 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 2 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 27 30 1 0 15 31 1 0 31 32 1 0 15 33 1 6 33 34 2 0 33 35 1 0 35 36 1 0 14 37 1 0 13 38 1 0 7 39 1 6 3 40 1 0 8 2 1 0 12 7 1 0 20 10 1 0 16 11 1 0 11 32 1 6 1 41 1 0 1 42 1 0 1 43 1 0 6 44 1 0 6 45 1 0 8 46 1 1 9 47 1 0 9 48 1 0 10 49 1 6 12 50 1 1 13 51 1 1 14 52 1 6 16 53 1 6 17 54 1 1 24 55 1 0 26 56 1 0 26 57 1 0 26 58 1 0 28 59 1 0 28 60 1 0 28 61 1 0 29 62 1 0 29 63 1 0 29 64 1 0 30 65 1 0 32 66 1 0 32 67 1 0 36 68 1 0 36 69 1 0 36 70 1 0 37 71 1 0 38 72 1 0 39 73 1 0 39 74 1 0 39 75 1 0 40 76 1 0 M END

Standard InCHIKey	KCVFVYXSNLKEHU-MBKFLBLHSA-N
Standard InCHI	InChI=1S/C28H36O12/c1-11(25(3,4)36)7-16(30)40-19-21-27-10-38-28(21,24(35)37-6)22(33)18(32)20(27)26(5)9-14(29)17(31)12(2)13(26)8-15(27)39-23(19)34/h7,13,15,18-22,31-33,36H,8-10H2,1-6H3/b11-7+/t13-,15+,18+,19+,20+,21+,22-,26-,27+,28+/m0/s1
SMILES	CC1=C(C(=O)C[C@]2([C@H]1C[C@@H]3[C@]45[C@@H]2[C@H]([C@@H]([C@@]([C@@H]4[C@H](C(=O)O3)OC(=O)/C=C(\C)/C(C)(C)O)(OC5)C(=O)OC)O)O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	564.22	Volume:	539.726 ? Van der Waals volume.
Dense:	1.045	LogP:	0.42 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.02 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.919 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	28.0
TPSA:	186.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.208	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.676	Fsp³:	0.714
MCE-18:	145.208 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.39	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? 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:	0.074	Promiscuous compounds:	0.385

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.908	MDCK Permeability:	-5.288
Pgp-inhibitor:	0.281	Pgp-substrate:	0.881
PAMPA:	0.82 ? 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):	0.024
20% Bioavailability (F20%):	0.043	30% Bioavailability (F30%):	0.717
50% Bioavailability (F50%):	0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.994
Plasma Protein Binding (PPB):	57.771%	Volume Distribution (VD):	-0.342
Fu:	44.721% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.006
BSEP inhibitor:	0.602

ADMET: Metabolism

CYP1A2-inhibitor:	0.997	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.793	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.045	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.027
CYP3A4-inhibitor:	0.956	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.211
HLM stability:	0.184 ? 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):

2.981

Half-life (T1/2):

3.185

ADMET: Toxicity

hERG Blockers:	0.005	hERG Blockers (10um):	0.01
Human Hepatotoxicity (H-HT):	0.791	Drug-induced Liver Injury (DILI):	0.936
AMES Toxicity:	0.808	Rat Oral Acute Toxicity:	0.364
Maximum Recommended Daily Dose:	0.333	Skin Sensitization:	1.0
Carcinogencity:	0.531	Eye Corrosion:	0.002
Eye Irritation:	0.502	Respiratory Toxicity:	0.342
Drug-induced Neurotoxicity:	0.163	Ototoxicity:	0.846
Hematotoxicity:	0.54	Drug-induced Nephrotoxicity:	0.985
Genotoxicity:	0.966	RPMI-8226 Immunitoxicity:	0.106
A549 Cytotoxicity:	0.017	Hek293 Cytotoxicity:	0.265
BCF:	0.52 ? 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:	3.304 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.152 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.364 ? 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
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	seed	n.a.	DOI[10.1016/0031-9422(96)00258-0]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1016/S1383-5769(99)00023-9]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10086989]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1512598]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[15165151]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	fruit	Indonesia	n.a.	PMID[17896817]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	Vietnam	n.a.	PMID[19026551]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	seeds	n.a.	n.a.	PMID[20050684]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[22506620]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[6481366]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7561896]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14948	Brucea javanica	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14948	Brucea javanica	Species	Simaroubaceae	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
Organism	4

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
NPT1355	Organism	Babesia gibsoni	Babesia gibsoni	IC50	=	0.107	ug/ml	PMID[17896817]
NPT992	Organism	Entamoeba histolytica	Entamoeba histolytica	IC50	=	0.279	ug/ml	DOI[10.1007/s00044-011-9767-1]
NPT474	Organism	Plasmodium berghei	Plasmodium berghei	Inhibition	=	40	%	PMID[3298551]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	0.005	ug/ml	PMID[3298551]

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 NPC476729 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	17125
0.1-0.2	31155
0.2-0.3	1506
0.3-0.4	16
0.4-0.5	15
0.5-0.6	23
0.6-0.7	9
0.7-0.8	0
0.8-0.85	4
0.85-0.9	1
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9155	High Similarity	NPC18945
0.9155	High Similarity	NPC152301
0.8784	High Similarity	NPC265557
0.8451	Intermediate Similarity	NPC143268
0.8333	Intermediate Similarity	NPC105926
0.8219	Intermediate Similarity	NPC323821
0.8108	Intermediate Similarity	NPC16081
0.7037	Intermediate Similarity	NPC67251
0.6667	Remote Similarity	NPC213084
0.6463	Remote Similarity	NPC146432
0.6463	Remote Similarity	NPC470778
0.6456	Remote Similarity	NPC268238
0.6456	Remote Similarity	NPC45218
0.6421	Remote Similarity	NPC251998
0.642	Remote Similarity	NPC479018
0.622	Remote Similarity	NPC89929
0.619	Remote Similarity	NPC480783
0.5955	Remote Similarity	NPC470779
0.5862	Remote Similarity	NPC480785
0.5854	Remote Similarity	NPC470776
0.5854	Remote Similarity	NPC17772
0.5843	Remote Similarity	NPC480777
0.5833	Remote Similarity	NPC262813
0.5747	Remote Similarity	NPC190185
0.5714	Remote Similarity	NPC295885
0.5698	Remote Similarity	NPC24651
0.5682	Remote Similarity	NPC312833
0.5682	Remote Similarity	NPC480787
0.5682	Remote Similarity	NPC480784
0.5647	Remote Similarity	NPC485623
0.5444	Remote Similarity	NPC94509
0.5444	Remote Similarity	NPC479017
0.5435	Remote Similarity	NPC480786
0.5368	Remote Similarity	NPC91693
0.5341	Remote Similarity	NPC476008
0.5312	Remote Similarity	NPC87662
0.5233	Remote Similarity	NPC470777
0.5196	Remote Similarity	NPC140045
0.5152	Remote Similarity	NPC190065
0.505	Remote Similarity	NPC141215

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476729 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6587
0.1-0.2	2537
0.2-0.3	26
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