NPASS Compound

Natural Product: NPC474466

Natural Product ID	NPC474466
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RGJSIZOZMBPAIL-YUVWTAJSSA-N
IUPAC Name	n.a.
Synonyms	6'-Dehydroxyghalakinoside; 6-Dehydroxyghalakinoside
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL469426
PubChem CID	16086566
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 81 87 0 0 0 0 0 0 0 0999 V2000 -0.0889 1.6384 2.7339 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8313 1.4108 1.6103 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5970 0.1599 0.8576 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5949 0.2190 -0.3345 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9857 0.0165 0.1272 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9165 0.1968 -0.9081 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1711 0.0712 -0.3073 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2639 0.8479 0.8610 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2951 0.4503 -1.2391 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.3346 0.9688 -0.4329 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8419 -0.8248 -1.8445 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7252 -1.7762 -2.1823 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9297 -2.1082 -1.1158 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3257 -1.3968 0.0403 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4362 -1.6606 1.0776 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1248 -1.3774 0.7282 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2787 -1.3088 2.0140 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8839 -1.1322 1.5293 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1424 -1.5820 2.5208 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5048 -1.7123 1.8077 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7940 -0.2734 1.3365 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7955 0.0784 0.3289 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2044 1.2836 -0.4844 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4416 0.8069 -1.2262 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7164 1.6425 -2.2670 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5669 0.7095 -0.2329 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2184 -0.0815 0.9910 C 0 0 1 0 0 0 0 0 0 0 0 0 3.9495 0.4566 2.0520 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8443 -1.4585 0.7368 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1954 -0.9822 0.1841 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7373 0.0195 -0.8588 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8561 0.8830 -1.2946 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1195 0.8293 -0.8232 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9220 1.8144 -1.4831 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1601 2.0868 -1.3250 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1115 2.4707 -2.3736 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8313 1.9270 -2.3168 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9584 2.1238 0.1296 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9639 -1.1993 -3.3444 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5674 1.2988 3.5192 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7021 2.2773 0.8861 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9054 1.5684 1.9301 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3521 -0.5535 -1.0726 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5199 1.2631 -0.7520 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3474 0.6914 0.9284 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6465 1.7364 0.6388 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0219 1.2073 -1.9724 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4549 0.3927 0.3718 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6512 -1.2750 -1.2566 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3038 -0.5240 -2.8303 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2180 -2.7328 -2.5261 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3329 -1.6662 0.3602 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6690 -2.0949 0.0477 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3658 -2.3016 2.4825 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6417 -0.5070 2.6721 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7844 -1.9030 0.6897 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1586 -2.5910 2.8764 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2618 -0.9489 3.3940 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3484 -2.3736 0.9579 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2003 -2.0501 2.5796 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6150 0.3078 2.2788 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7752 -0.7691 -0.4296 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4405 1.5607 -1.2072 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5392 2.1167 0.1682 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2167 -0.2360 -1.5960 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4003 1.2056 -3.1146 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2875 0.8678 2.6728 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3485 -2.0077 -0.0604 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9983 -1.9956 1.6788 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7996 -0.5128 0.9849 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7559 -1.8249 -0.2585 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3905 -0.6312 -1.7241 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4566 0.1436 -0.0655 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1334 2.7626 -2.0841 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5873 1.5218 -3.3352 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5209 2.2869 1.1699 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0475 2.2770 0.2133 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4252 2.8774 -0.4829 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4285 -1.5641 -4.2835 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0660 -0.0761 -3.3912 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8920 -1.4617 -3.3315 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 1 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 1 7 9 1 0 9 10 1 0 9 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 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 27 28 1 1 27 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 34 36 1 0 36 37 1 0 26 38 1 1 12 39 1 0 18 3 1 0 27 21 1 0 37 32 1 0 22 3 1 0 31 26 1 0 16 5 1 0 14 7 1 0 1 40 1 0 2 41 1 0 2 42 1 0 4 43 1 0 4 44 1 0 5 45 1 1 8 46 1 0 9 47 1 6 10 48 1 0 11 49 1 0 11 50 1 0 12 51 1 6 14 52 1 1 16 53 1 6 17 54 1 0 17 55 1 0 18 56 1 6 19 57 1 0 19 58 1 0 20 59 1 0 20 60 1 0 21 61 1 1 22 62 1 6 23 63 1 0 23 64 1 0 24 65 1 6 25 66 1 0 28 67 1 0 29 68 1 0 29 69 1 0 30 70 1 0 30 71 1 0 31 72 1 6 33 73 1 0 37 74 1 0 37 75 1 0 38 76 1 0 38 77 1 0 38 78 1 0 39 79 1 0 39 80 1 0 39 81 1 0 M END

Standard InCHIKey	RGJSIZOZMBPAIL-YUVWTAJSSA-N
Standard InCHI	InChI=1S/C29H42O10/c1-14-7-23(32)29(35)25(37-14)38-20-9-16-3-4-18-19(27(16,13-30)11-21(20)39-29)10-22(31)26(2)17(5-6-28(18,26)34)15-8-24(33)36-12-15/h8,14,16-23,25,30-32,34-35H,3-7,9-13H2,1-2H3/t14-,16+,17-,18-,19+,20-,21-,22-,23-,25+,26+,27-,28+,29+/m1/s1
SMILES	OC[C@]12C[C@H]3O[C@@]4(O)[C@H](O)C[C@H](O[C@H]4O[C@@H]3C[C@@H]1CC[C@@H]1[C@@H]2C[C@@H](O)[C@]2([C@]1(O)CC[C@@H]2C1=CC(=O)OC1)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	550.28	Volume:	532.874 ? Van der Waals volume.
Dense:	1.033	LogP:	0.52 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.221 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.715 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	36.0
TPSA:	155.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.246	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.77	Fsp³:	0.897
MCE-18:	127.636 ? 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:	0.417	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.018 ? 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:	0.149	Promiscuous compounds:	0.921

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.593	MDCK Permeability:	-5.03
Pgp-inhibitor:	0.0	Pgp-substrate:	0.999
PAMPA:	1.0 ? 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%):	0.724	30% Bioavailability (F30%):	0.563
50% Bioavailability (F50%):	0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.042	MRP1:	0.547
Plasma Protein Binding (PPB):	40.393%	Volume Distribution (VD):	-0.332
Fu:	61.276% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.967
OATP1B3 inhibitor:	0.264	BCRP inhibitor:	0.09
BSEP inhibitor:	0.057

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.006	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.046	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.01
HLM stability:	0.039 ? 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):

3.008

Half-life (T1/2):

3.502

ADMET: Toxicity

hERG Blockers:	0.116	hERG Blockers (10um):	0.589
Human Hepatotoxicity (H-HT):	0.735	Drug-induced Liver Injury (DILI):	0.722
AMES Toxicity:	0.975	Rat Oral Acute Toxicity:	0.997
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.966	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.997
Drug-induced Neurotoxicity:	0.103	Ototoxicity:	0.927
Hematotoxicity:	0.813	Drug-induced Nephrotoxicity:	0.995
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.959
A549 Cytotoxicity:	0.651	Hek293 Cytotoxicity:	0.991
BCF:	0.539 ? 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:	3.166 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.591 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.728 ? 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
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	roots	Wadi Um Hebal, Egypt	2001-JAN	PMID[16989527]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19555122]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	Aerial Parts	n.a.	n.a.	PMID[30629433]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Activity	1
IC50	12

Activity Type	# Activity
Cell line	10
Others	2
Non-molecular	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
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	50.0	nM	PMID[12825928]
NPT1081	Cell line	BXPC-3	Homo sapiens	IC50	=	300.0	nM	PMID[22703163]
NPT114	Cell line	LoVo	Homo sapiens	IC50	=	300.0	nM	PMID[24328283]
NPT81	Cell line	A549	Homo sapiens	IC50	=	50.0	nM	PMID[27025343]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	300.0	nM	PMID[27020525]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	600.0	nM	PMID[30629433]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	7000.0	nM	PMID[30629433]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	5000.0	nM	PMID[30629433]
NPT1307	Cell line	Calu-1	Homo sapiens	IC50	=	6000.0	nM	PMID[30629433]
NPT380	Cell line	U-251	Homo sapiens	IC50	=	8000.0	nM	PMID[30629433]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	400.0	nM	PMID[19555122]
NPT2	Others	Unspecified	n.a.	Activity	=	45.0	%	PMID[16562830]
NPT2	Others	Unspecified	n.a.	IC50	=	700.0	nM	PMID[27072906]

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 NPC474466 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	16299
0.1-0.2	30129
0.2-0.3	3185
0.3-0.4	133
0.4-0.5	76
0.5-0.6	18
0.6-0.7	10
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8875	High Similarity	NPC475136
0.8395	Intermediate Similarity	NPC488162
0.8395	Intermediate Similarity	NPC93416
0.7558	Intermediate Similarity	NPC488158
0.7558	Intermediate Similarity	NPC488159
0.7326	Intermediate Similarity	NPC329905
0.6977	Remote Similarity	NPC253456
0.6977	Remote Similarity	NPC159338
0.6897	Remote Similarity	NPC488160
0.6452	Remote Similarity	NPC488163
0.6374	Remote Similarity	NPC488161
0.6374	Remote Similarity	NPC16569
0.6292	Remote Similarity	NPC104585
0.6264	Remote Similarity	NPC42670
0.6264	Remote Similarity	NPC19124
0.6098	Remote Similarity	NPC196471
0.5957	Remote Similarity	NPC157817
0.5806	Remote Similarity	NPC471353
0.5638	Remote Similarity	NPC277374
0.5542	Remote Similarity	NPC189588
0.5521	Remote Similarity	NPC609258
0.5455	Remote Similarity	NPC225385
0.5402	Remote Similarity	NPC475030
0.5368	Remote Similarity	NPC171619
0.5288	Remote Similarity	NPC476221
0.5288	Remote Similarity	NPC477709
0.5204	Remote Similarity	NPC91
0.5204	Remote Similarity	NPC79193
0.5155	Remote Similarity	NPC471359
0.5155	Remote Similarity	NPC179412
0.5155	Remote Similarity	NPC471356
0.51	Remote Similarity	NPC163365
0.5049	Remote Similarity	NPC470094
0.5049	Remote Similarity	NPC208193

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474466 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6571
0.1-0.2	2507
0.2-0.3	58
0.3-0.4	6
0.4-0.5	4
0.5-0.6	3
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
0.5758	Remote Similarity	NPD7625	Phase 1
0.5208	Remote Similarity	NPD8335	Phase 4
0.5155	Remote Similarity	NPD8380	Approved

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