NPASS Compound

Natural Product: NPC49371

Natural Product ID	NPC49371
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cucurbitacin R
IUPAC Name	(2S,8S,9R,10R,13R,14S,16R,17R)-17-[(2R)-2,6-dihydroxy-6-methyl-3-oxoheptan-2-yl]-2,16-dihydroxy-4,4,9,13,14-pentamethyl-2,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthrene-3,11-dione
Synonyms	Cucurbitacin R
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL564629
PubChem CID	180535
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 83 86 0 0 0 0 0 0 0 0999 V2000 8.2548 -1.0965 -0.7933 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0772 -0.1084 -0.6273 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7452 1.2541 -0.4638 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3610 -0.5335 0.6003 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1788 0.2458 1.0171 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0450 0.2554 0.1085 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0306 -0.4298 -0.8946 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8105 1.1317 0.3731 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8496 2.1078 -0.8125 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6917 0.2009 0.2701 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7879 -0.9079 1.2764 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3823 -1.4942 1.4589 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3522 -0.8177 0.3238 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2286 -1.5257 -0.9000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8383 -0.8346 0.3973 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3751 -1.8506 -0.6231 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8510 -1.8552 -0.7067 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5356 -0.7281 -0.6516 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7986 0.5176 -0.5049 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.7820 1.5465 0.0113 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8743 1.7781 -1.0392 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.6591 0.5316 -1.0378 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8477 0.5789 -1.2795 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0166 -0.7361 -0.7500 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6360 -1.4049 0.4698 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3705 -1.6679 -1.9273 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6451 2.8466 -0.5394 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5888 0.4351 0.4084 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2420 0.6485 1.7870 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7675 1.6094 -0.0090 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1256 2.7582 0.0757 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3792 1.4020 -0.5867 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2831 0.5807 0.4496 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0543 1.2171 1.7761 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7540 -1.8421 1.0517 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0894 1.7758 1.5299 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3392 -0.1215 -1.7748 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8006 -0.7968 -1.6923 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8512 -2.1160 -0.8797 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9043 -0.9945 0.1078 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5649 1.2778 -1.2344 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0279 2.0439 -0.7400 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2227 1.3824 0.5127 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0626 -1.6059 0.4743 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0652 -0.5583 1.4859 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4353 1.3390 1.2121 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7945 -0.0750 2.0381 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4194 1.6275 -1.7200 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9037 2.3432 -1.0769 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3699 3.0638 -0.5606 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7794 -0.1431 -0.8071 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9932 -0.3941 2.2631 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5230 -2.5960 1.2370 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0294 -1.4402 2.4342 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3353 -2.4751 -1.1229 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2294 -2.0182 -0.6880 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2090 -0.9481 -1.8139 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0476 -1.3778 1.3758 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0906 -2.8798 -0.2876 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0247 -1.5942 -1.6443 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3978 -2.7755 -0.8152 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4901 0.8689 -1.5198 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3426 1.1756 0.9019 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3973 2.5158 0.2619 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4579 2.0553 -2.0151 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2152 -1.0878 1.4201 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7095 -1.1051 0.4784 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6358 -2.5257 0.3302 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9185 -1.1277 -2.7274 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4365 -2.0303 -2.3984 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0054 -2.5042 -1.6301 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2928 2.5251 0.1453 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5765 1.6623 1.9363 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5961 0.3230 2.6186 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0714 -0.1205 1.8094 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5710 0.9005 -1.5552 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0977 2.3476 -0.8205 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2466 0.5468 2.5975 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7368 2.0275 1.7649 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9222 1.7646 2.2001 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9849 -2.2843 1.9086 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4224 2.7042 1.3161 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7633 -0.6034 -2.5444 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 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 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 24 26 1 0 21 27 1 0 19 28 1 0 28 29 1 1 28 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 33 34 1 1 11 35 1 0 8 36 1 1 2 37 1 0 33 10 1 0 33 13 1 0 28 15 1 0 24 18 1 0 1 38 1 0 1 39 1 0 1 40 1 0 3 41 1 0 3 42 1 0 3 43 1 0 4 44 1 0 4 45 1 0 5 46 1 0 5 47 1 0 9 48 1 0 9 49 1 0 9 50 1 0 10 51 1 6 11 52 1 1 12 53 1 0 12 54 1 0 14 55 1 0 14 56 1 0 14 57 1 0 15 58 1 1 16 59 1 0 16 60 1 0 17 61 1 0 19 62 1 6 20 63 1 0 20 64 1 0 21 65 1 6 25 66 1 0 25 67 1 0 25 68 1 0 26 69 1 0 26 70 1 0 26 71 1 0 27 72 1 0 29 73 1 0 29 74 1 0 29 75 1 0 32 76 1 0 32 77 1 0 34 78 1 0 34 79 1 0 34 80 1 0 35 81 1 0 36 82 1 0 37 83 1 0 M END

Standard InCHIKey	ITMUUFDDBRYVNJ-VOKXYEOFSA-N
Standard InCHI	InChI=1S/C30H46O7/c1-25(2,36)12-11-21(33)30(8,37)23-19(32)14-27(5)20-10-9-16-17(13-18(31)24(35)26(16,3)4)29(20,7)22(34)15-28(23,27)6/h9,17-20,23,31-32,36-37H,10-15H2,1-8H3/t17-,18+,19-,20+,23+,27+,28-,29+,30+/m1/s1
SMILES	CC(C)(CCC(=O)[C@@](C)([C@H]1[C@@H](C[C@@]2(C)[C@@H]3CC=C4[C@@H](C[C@@H](C(=O)C4(C)C)O)[C@]3(C)C(=O)C[C@]12C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	518.32	Volume:	544.196 ? Van der Waals volume.
Dense:	0.952	LogP:	1.57 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.057 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.724 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	23.0
TPSA:	132.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.411	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.336	Fsp³:	0.833
MCE-18:	96.436 ? 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:	0.691	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? 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:	0.312	Promiscuous compounds:	0.622

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.026	MDCK Permeability:	-4.767
Pgp-inhibitor:	0.005	Pgp-substrate:	0.196
PAMPA:	0.996 ? 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):	0.002
20% Bioavailability (F20%):	0.024	30% Bioavailability (F30%):	0.041
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.237	MRP1:	0.982
Plasma Protein Binding (PPB):	82.413%	Volume Distribution (VD):	-0.022
Fu:	21.779% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.204
BSEP inhibitor:	0.98

ADMET: Metabolism

CYP1A2-inhibitor:	0.112	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.017	CYP2C19-substrate:	0.013
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.313
CYP3A4-inhibitor:	0.834	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.98
HLM stability:	0.045 ? 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):

6.39

Half-life (T1/2):

1.251

ADMET: Toxicity

hERG Blockers:	0.015	hERG Blockers (10um):	0.099
Human Hepatotoxicity (H-HT):	0.612	Drug-induced Liver Injury (DILI):	0.306
AMES Toxicity:	0.671	Rat Oral Acute Toxicity:	0.703
Maximum Recommended Daily Dose:	0.78	Skin Sensitization:	0.984
Carcinogencity:	0.856	Eye Corrosion:	0.0
Eye Irritation:	0.042	Respiratory Toxicity:	0.879
Drug-induced Neurotoxicity:	0.321	Ototoxicity:	0.706
Hematotoxicity:	0.808	Drug-induced Nephrotoxicity:	0.947
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.375
A549 Cytotoxicity:	0.401	Hek293 Cytotoxicity:	0.397
BCF:	0.487 ? 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:	3.148 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.602 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.847 ? 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
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33269591]
NPO32650	conobea scoparioides	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7852999]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21876	Trichosanthes cucumeroides	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
IC50	1
Inhibition	7

Activity Type	# Activity
Individual protein	1
Cell line	4
Others	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2536	Individual protein	Leukocyte adhesion glycoprotein LFA-1 alpha	Homo sapiens	IC50	>	50000.0	nM	PMID[19506058]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4306	Cell line	JY	Homo sapiens	Inhibition	=	20.0	%	PMID[15043411]
NPT4306	Cell line	JY	Homo sapiens	Inhibition	=	22.0	%	PMID[22194678]
NPT4306	Cell line	JY	Homo sapiens	Inhibition	=	74.0	%	PMID[22194678]
NPT4306	Cell line	JY	Homo sapiens	Inhibition	=	7.0	%	PMID[22683222]
NPT2	Others	Unspecified	n.a.	Inhibition	=	86.0	%	PMID[8988604]
NPT2	Others	Unspecified	n.a.	Inhibition	=	82.8	%	PMID[19506058]
NPT2	Others	Unspecified	n.a.	Inhibition	=	79.2	%	PMID[19506058]

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 NPC49371 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	22875
0.1-0.2	25601
0.2-0.3	1302
0.3-0.4	39
0.4-0.5	13
0.5-0.6	15
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC479419
0.8033	Intermediate Similarity	NPC117185
0.7727	Intermediate Similarity	NPC196528
0.746	Intermediate Similarity	NPC191892
0.746	Intermediate Similarity	NPC311612
0.6923	Remote Similarity	NPC479420
0.6714	Remote Similarity	NPC100267
0.6714	Remote Similarity	NPC475524
0.6667	Remote Similarity	NPC474720
0.6032	Remote Similarity	NPC488647
0.5968	Remote Similarity	NPC479417
0.5942	Remote Similarity	NPC165873
0.589	Remote Similarity	NPC486346
0.5811	Remote Similarity	NPC280782
0.5797	Remote Similarity	NPC87351
0.5714	Remote Similarity	NPC488644
0.5634	Remote Similarity	NPC488646
0.5493	Remote Similarity	NPC214644
0.5455	Remote Similarity	NPC239273
0.5278	Remote Similarity	NPC58370
0.5278	Remote Similarity	NPC43285
0.5238	Remote Similarity	NPC42675
0.5195	Remote Similarity	NPC304495
0.5128	Remote Similarity	NPC475294
0.5068	Remote Similarity	NPC185

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC49371 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7670
0.1-0.2	1459
0.2-0.3	21
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