NPASS Compound

Natural Product: NPC153440

Natural Product ID	NPC153440
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Withanolide F
IUPAC Name	(2R)-2-[(1S)-1-[(8R,9S,10R,13S,14R,17S)-14,17-dihydroxy-10,13-dimethyl-1-oxo-4,7,8,9,11,12,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-1-hydroxyethyl]-4,5-dimethyl-2,3-dihydropyran-6-one
Synonyms	Withanolide F
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL488913
PubChem CID	44562999
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides 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 72 76 0 0 0 0 0 0 0 0999 V2000 7.0557 0.5882 -1.0403 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8374 0.7996 -0.2013 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9605 1.5170 0.8764 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2393 2.1336 1.3167 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7745 1.7333 1.6966 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8179 2.4180 2.7565 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6051 1.1512 1.2539 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5180 0.0870 0.3643 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5835 0.1623 -0.6720 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1034 0.1271 -0.2674 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0898 -0.9172 -1.3068 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1133 0.0623 0.8316 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1477 -1.2044 1.6373 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2690 -1.7741 1.6480 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9658 -1.0774 0.5527 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4581 -1.0322 0.6423 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9910 -2.4226 0.3202 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2406 -2.4052 -0.4720 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9192 -1.3426 -0.7973 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1519 -1.4455 -1.5913 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3191 -0.3711 -2.5700 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7622 0.7999 -2.3988 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9618 1.0622 -1.2289 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6946 2.2441 -0.9106 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4231 -0.0147 -0.3576 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9141 0.2517 1.0443 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9269 -0.1091 -0.4468 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2401 1.2007 -0.5363 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7245 0.9571 -0.7020 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3067 0.2850 0.5598 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8943 1.1581 1.6812 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7222 -1.6646 -0.7117 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5265 1.0863 1.7359 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0685 1.3785 -0.8806 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2270 1.5564 -1.5944 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9134 -0.1865 -1.8077 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9036 0.4121 -0.3729 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9006 2.3543 0.4562 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6978 1.4322 2.0490 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0181 3.1088 1.8127 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5936 -0.9144 0.8827 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2407 0.7375 -1.5563 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9004 -0.8882 -0.9557 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3976 -0.6983 -2.1470 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9865 -1.9558 -0.9436 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0919 -0.9350 -1.8402 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8730 -1.9471 1.2479 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4153 -1.0594 2.7058 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7836 -1.5621 2.6044 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2418 -2.8850 1.5536 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8662 -0.8073 1.6411 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2583 -3.0338 -0.2390 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2132 -3.0009 1.2531 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6078 -3.3670 -0.8011 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0610 -1.5624 -0.9459 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1382 -2.4132 -2.1810 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9122 -0.5441 -3.4495 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8890 1.6073 -3.1361 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9693 -0.6883 1.6318 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9773 0.6165 0.9685 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2882 1.0189 1.5395 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7056 -0.6502 -1.4159 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5310 1.6586 -1.5083 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4624 1.9346 0.2335 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6600 0.3572 -1.6145 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3069 1.9891 -0.8146 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8173 2.2375 1.4013 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2814 0.9502 2.6033 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9206 0.9492 1.9248 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2947 -2.5539 -0.5046 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3808 1.9704 1.3472 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0899 1.3397 -1.8541 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 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 8 10 1 0 10 11 1 0 10 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 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 1 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 1 15 32 1 6 12 33 1 1 10 34 1 6 9 2 1 0 30 12 1 0 30 15 1 0 27 16 1 0 25 19 1 0 1 35 1 0 1 36 1 0 1 37 1 0 4 38 1 0 4 39 1 0 4 40 1 0 8 41 1 1 9 42 1 0 9 43 1 0 11 44 1 0 11 45 1 0 11 46 1 0 13 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 16 51 1 1 17 52 1 0 17 53 1 0 18 54 1 0 20 55 1 0 20 56 1 0 21 57 1 0 22 58 1 0 26 59 1 0 26 60 1 0 26 61 1 0 27 62 1 6 28 63 1 0 28 64 1 0 29 65 1 0 29 66 1 0 31 67 1 0 31 68 1 0 31 69 1 0 32 70 1 0 33 71 1 0 34 72 1 0 M END

Standard InCHIKey	GQHHHBATDOXAEP-MEZCUPPISA-N
Standard InCHI	InChI=1S/C28H38O6/c1-16-15-22(34-23(30)17(16)2)26(5,31)28(33)14-13-27(32)20-10-9-18-7-6-8-21(29)25(18,4)19(20)11-12-24(27,28)3/h6,8-9,19-20,22,31-33H,7,10-15H2,1-5H3/t19-,20+,22+,24-,25-,26-,27+,28-/m0/s1
SMILES	CC1=C(C)C(=O)O[C@H](C1)[C@@](C)([C@@]1(CC[C@]2([C@@H]3CC=C4CC=CC(=O)[C@]4(C)[C@H]3CC[C@]12C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.27	Volume:	489.621 ? Van der Waals volume.
Dense:	0.96	LogP:	1.632 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.107 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.984 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	28.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.421	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.301	Fsp³:	0.714
MCE-18:	98.167 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.269	Fluc inhibitor:	0.122 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.016 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.439	Promiscuous compounds:	0.318

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.224	MDCK Permeability:	-4.865
Pgp-inhibitor:	0.001	Pgp-substrate:	0.903
PAMPA:	0.988 ? 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):	0.013
20% Bioavailability (F20%):	0.732	30% Bioavailability (F30%):	0.719
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.385	MRP1:	0.993
Plasma Protein Binding (PPB):	94.22%	Volume Distribution (VD):	0.101
Fu:	4.823% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.07
BSEP inhibitor:	0.945

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.032
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.944	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.173	CYP2D6-substrate:	0.005
CYP3A4-inhibitor:	0.101	CYP3A4-substrate:	0.995
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	1.0
HLM stability:	0.978 ? 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):

5.069

Half-life (T1/2):

2.482

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.156
Human Hepatotoxicity (H-HT):	0.741	Drug-induced Liver Injury (DILI):	0.222
AMES Toxicity:	0.337	Rat Oral Acute Toxicity:	0.351
Maximum Recommended Daily Dose:	0.769	Skin Sensitization:	0.985
Carcinogencity:	0.93	Eye Corrosion:	0.011
Eye Irritation:	0.51	Respiratory Toxicity:	0.593
Drug-induced Neurotoxicity:	0.185	Ototoxicity:	0.361
Hematotoxicity:	0.225	Drug-induced Nephrotoxicity:	0.715
Genotoxicity:	0.975	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.212	Hek293 Cytotoxicity:	0.466
BCF:	0.579 ? 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:	3.213 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.711 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.073 ? 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
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	fruits	n.a.	n.a.	PMID[18952419]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23316950]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28617598]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30649869]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	Whole Fruits	n.a.	n.a.	PMID[32159343]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28734	Physalis peruviana	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28734	Physalis peruviana	Species	Solanaceae	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	10
Inhibition	2
Activity	2
Survival	2

Activity Type	# Activity
Individual protein	1
Cell line	10
Others	3
Organism	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2601	Individual protein	NF-kappaB inhibitor alpha	Homo sapiens	IC50	>	50000.0	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	10900.0	nM	PMID[16300945]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	84.6	%	PMID[17696332]
NPT858	Cell line	LNCaP	Homo sapiens	IC50	=	130.0	nM	PMID[28617598]
NPT1629	Cell line	CWR22R	Homo sapiens	IC50	=	70.0	nM	PMID[28617598]
NPT369	Cell line	ACHN	Homo sapiens	IC50	>	2000.0	nM	PMID[28617598]
NPT387	Cell line	M14	Homo sapiens	IC50	>	2000.0	nM	PMID[28617598]
NPT170	Cell line	SK-MEL-28	Homo sapiens	IC50	>	2000.0	nM	PMID[28617598]
NPT859	Cell line	HFF	Homo sapiens	IC50	>	2000.0	nM	PMID[28617598]
NPT2	Others	Unspecified	n.a.	IC50	=	5700.0	nM	PMID[8158155]
NPT2	Others	Unspecified	n.a.	Inhibition	=	90.8	%	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	2000.0	nM	PMID[20541427]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT71	Cell line	HEK293	Homo sapiens	Survival	=	100.0	%	PubChem BioAssay data set
NPT113	Cell line	RAW264.7	Mus musculus	Survival	=	100.0	%	PMID[8389875]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	24.9	%	PMID[23398362]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	18.2	%	PMID[23145909]

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 NPC153440 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	18834
0.1-0.2	26633
0.2-0.3	4210
0.3-0.4	126
0.4-0.5	24
0.5-0.6	10
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.875	High Similarity	NPC107493
0.8615	High Similarity	NPC103045
0.7857	Intermediate Similarity	NPC5292
0.7647	Intermediate Similarity	NPC79579
0.75	Intermediate Similarity	NPC484742
0.75	Intermediate Similarity	NPC225826
0.7246	Intermediate Similarity	NPC190286
0.7	Intermediate Similarity	NPC270850
0.7	Intermediate Similarity	NPC176840
0.7	Intermediate Similarity	NPC305260
0.6933	Remote Similarity	NPC484718
0.68	Remote Similarity	NPC484717
0.6351	Remote Similarity	NPC46570
0.6351	Remote Similarity	NPC44428
0.6351	Remote Similarity	NPC78691
0.6216	Remote Similarity	NPC191620
0.6216	Remote Similarity	NPC158285
0.6098	Remote Similarity	NPC173347
0.6053	Remote Similarity	NPC470961
0.6	Remote Similarity	NPC484725
0.5921	Remote Similarity	NPC125794
0.5921	Remote Similarity	NPC171401
0.5844	Remote Similarity	NPC285729
0.5789	Remote Similarity	NPC484743
0.55	Remote Similarity	NPC484745
0.5316	Remote Similarity	NPC29133
0.5287	Remote Similarity	NPC484715
0.5185	Remote Similarity	NPC5073
0.5122	Remote Similarity	NPC474585
0.5063	Remote Similarity	NPC486565

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC153440 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6798
0.1-0.2	2196
0.2-0.3	156
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