NPASS Compound

Natural Product: NPC157376

Natural Product ID	NPC157376
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Convallatoxol
IUPAC Name	3-[(3S,5S,8R,9S,10R,13R,14S,17R)-5,14-dihydroxy-10-(hydroxymethyl)-13-methyl-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
Synonyms	Convallatoxol
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1170234
PubChem CID	49799113
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 83 88 0 0 0 0 0 0 0 0999 V2000 -0.1994 1.3630 -2.2995 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4646 1.4297 -1.1104 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1514 0.2472 -0.1772 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9658 0.5020 1.0595 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0906 -0.4145 1.3298 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8451 -0.9637 0.1846 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0422 -1.1557 -1.0754 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5753 -0.9732 -0.9273 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0469 -0.8419 -2.2360 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0046 -2.2520 -0.3809 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4656 -2.2304 -0.6598 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0757 -0.8552 -0.6294 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3278 0.1613 0.1314 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0363 1.4751 0.0367 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 1.3338 -0.4854 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2219 0.2333 0.1573 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4524 -1.0448 -0.0269 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1251 -1.9124 -0.9031 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4027 -1.7546 1.3069 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3898 -1.0131 2.1999 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4121 0.3998 1.6492 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7086 1.0199 1.9978 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6699 0.5003 2.7414 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8050 1.4178 2.8612 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8812 1.2653 3.4808 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4351 2.5286 2.1242 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1580 2.3690 1.5692 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5686 0.1216 -0.4900 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0681 -0.3323 -0.0842 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1693 -1.1265 0.0425 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7928 -1.2866 -1.2059 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1266 -0.0922 -1.7893 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1690 0.2760 -2.9149 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2015 1.0830 -0.8741 C 0 0 1 0 0 0 0 0 0 0 0 0 6.8729 0.6728 0.3983 C 0 0 2 0 0 0 0 0 0 0 0 0 6.1382 -0.5132 1.0187 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5105 -0.0423 2.1530 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9387 1.7445 1.2876 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0269 2.0356 -1.4873 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2815 1.9000 -2.9673 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5635 1.2956 -1.3476 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4394 2.3938 -0.5783 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2516 0.4390 1.9359 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3220 1.5744 1.1303 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8207 0.1413 1.9713 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7363 -1.2298 2.0366 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1572 -2.0145 0.4772 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3940 -0.4682 -1.9002 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2001 -2.1721 -1.5232 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3726 -1.6106 -2.7812 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5270 -3.0874 -0.9246 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1640 -2.4203 0.6759 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9506 -2.9360 0.0699 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6404 -2.6846 -1.6569 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2212 -0.5061 -1.6743 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3726 -0.1305 1.2250 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1346 1.9878 1.0377 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5723 2.2201 -0.6204 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4764 1.1856 -1.5805 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9718 2.2996 -0.2961 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7580 -1.8650 -1.8236 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7724 -2.7986 1.2513 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4184 -1.7860 1.7718 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3789 -1.5091 2.1896 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0367 -0.9833 3.2408 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5864 0.9893 2.0551 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7048 -0.4684 3.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4569 3.0971 2.0383 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2101 2.4912 0.4903 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4060 0.1236 0.2632 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6618 -0.8194 -1.0616 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7221 0.9329 -1.2487 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9523 -2.1612 0.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1345 -0.2273 -2.2638 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7118 -0.6642 -3.2770 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7331 0.7144 -3.7562 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4122 1.0120 -2.5712 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2357 1.5939 -0.6991 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9035 0.3464 0.2023 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8842 -1.2736 1.3839 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1929 0.2283 2.8168 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8558 1.8395 1.6739 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8143 1.6355 -1.9212 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 6 8 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 6 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 16 28 1 6 6 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 35 38 1 0 34 39 1 0 13 3 1 0 21 16 1 0 27 22 1 0 36 30 1 0 8 3 1 0 17 12 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 0 5 46 1 0 6 47 1 1 7 48 1 0 7 49 1 0 9 50 1 0 10 51 1 0 10 52 1 0 11 53 1 0 11 54 1 0 12 55 1 6 13 56 1 1 14 57 1 0 14 58 1 0 15 59 1 0 15 60 1 0 18 61 1 0 19 62 1 0 19 63 1 0 20 64 1 0 20 65 1 0 21 66 1 1 23 67 1 0 27 68 1 0 27 69 1 0 28 70 1 0 28 71 1 0 28 72 1 0 30 73 1 1 32 74 1 6 33 75 1 0 33 76 1 0 33 77 1 0 34 78 1 1 35 79 1 6 36 80 1 1 37 81 1 0 38 82 1 0 39 83 1 0 M END

Standard InCHIKey	UQEKVLJMBGSQGS-MIXAURORSA-N
Standard InCHI	InChI=1S/C29H44O10/c1-15-22(32)23(33)24(34)25(38-15)39-17-3-8-27(14-30)19-4-7-26(2)18(16-11-21(31)37-13-16)6-10-29(26,36)20(19)5-9-28(27,35)12-17/h11,15,17-20,22-25,30,32-36H,3-10,12-14H2,1-2H3/t15-,17-,18+,19-,20+,22-,23+,24+,25+,26+,27-,28-,29-/m0/s1
SMILES	OC[C@@]12CC[C@@H](C[C@@]2(O)CC[C@@H]2[C@@H]1CC[C@]1([C@]2(O)CC[C@@H]1C1=CC(=O)OC1)C)O[C@H]1O[C@@H](C)[C@@H]([C@H]([C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	552.29	Volume:	541.431 ? Van der Waals volume.
Dense:	1.02	LogP:	0.405 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.137 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.634 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	32.0
TPSA:	166.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.214	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.324	Fsp³:	0.897
MCE-18:	116.291 ? 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:	0.716	Fluc inhibitor:	0.002 ? 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:	0.143	Promiscuous compounds:	0.428

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.715	MDCK Permeability:	-5.239
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):	0.443
20% Bioavailability (F20%):	0.898	30% Bioavailability (F30%):	0.939
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.303	MRP1:	0.78
Plasma Protein Binding (PPB):	52.743%	Volume Distribution (VD):	-0.461
Fu:	47.651% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.954
OATP1B3 inhibitor:	0.955	BCRP inhibitor:	0.045
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.297	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.991	CYP3A4-substrate:	0.012
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.112
HLM stability:	0.004 ? 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):

1.83

Half-life (T1/2):

3.345

ADMET: Toxicity

hERG Blockers:	0.15	hERG Blockers (10um):	0.578
Human Hepatotoxicity (H-HT):	0.796	Drug-induced Liver Injury (DILI):	0.472
AMES Toxicity:	0.876	Rat Oral Acute Toxicity:	0.96
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.929	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.993
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.771
Hematotoxicity:	0.639	Drug-induced Nephrotoxicity:	0.977
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.861
A549 Cytotoxicity:	0.948	Hek293 Cytotoxicity:	0.994
BCF:	0.631 ? 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:	3.165 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.423 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.727 ? 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
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20553004]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	latex	Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Yunnan Province, China	2011-Mar	PMID[24033101]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	trunk bark	Yunnan, China	n.a.	PMID[24582402]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8369	Antiaris toxicaria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8369	Antiaris toxicaria	Species	Moraceae	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
Activity	4
Ratio	2
Inhibition	1
ED50	10

Activity Type	# Activity
Cell line	7
Non-molecular	10

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
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	0.014	ug ml-1	PMID[22148880]
NPT308	Cell line	CAKI-1	Homo sapiens	ED50	=	0.0061	ug ml-1	PMID[22148880]
NPT309	Cell line	1A9	Homo sapiens	ED50	=	0.0076	ug ml-1	PMID[22148880]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	0.013	ug ml-1	PMID[18077425]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.012	ug ml-1	PMID[18077425]
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.004	ug ml-1	PMID[18077425]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.025	ug ml-1	PMID[18077425]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.1	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.25	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	138.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	625.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	5.0	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	20.0	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	80.7	%	PMID[24033101]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.02	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.036	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.014	ug ml-1	PMID[24582402]

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 NPC157376 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	15115
0.1-0.2	28746
0.2-0.3	5319
0.3-0.4	466
0.4-0.5	68
0.5-0.6	65
0.6-0.7	53
0.7-0.8	0
0.8-0.85	7
0.85-0.9	4
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC142066
1.0	High Similarity	NPC603972
0.863	High Similarity	NPC99728
0.863	High Similarity	NPC87250
0.863	High Similarity	NPC244402
0.863	High Similarity	NPC50305
0.84	Intermediate Similarity	NPC17896
0.84	Intermediate Similarity	NPC469755
0.84	Intermediate Similarity	NPC284406
0.84	Intermediate Similarity	NPC197707
0.84	Intermediate Similarity	NPC251866
0.8205	Intermediate Similarity	NPC471354
0.8205	Intermediate Similarity	NPC27507
0.7792	Intermediate Similarity	NPC84987
0.7595	Intermediate Similarity	NPC76572
0.7595	Intermediate Similarity	NPC193382
0.7436	Intermediate Similarity	NPC99620
0.7308	Intermediate Similarity	NPC158344
0.7284	Intermediate Similarity	NPC77319
0.7284	Intermediate Similarity	NPC471351
0.7284	Intermediate Similarity	NPC471355
0.725	Intermediate Similarity	NPC469750
0.7125	Intermediate Similarity	NPC219085
0.7125	Intermediate Similarity	NPC309034
0.7045	Intermediate Similarity	NPC469749
0.6988	Remote Similarity	NPC9499
0.6988	Remote Similarity	NPC471360
0.6988	Remote Similarity	NPC469751
0.6988	Remote Similarity	NPC471361
0.6988	Remote Similarity	NPC86159
0.6988	Remote Similarity	NPC469752
0.6988	Remote Similarity	NPC469754
0.6988	Remote Similarity	NPC70542
0.6897	Remote Similarity	NPC32793
0.6897	Remote Similarity	NPC116075
0.6875	Remote Similarity	NPC474418
0.6867	Remote Similarity	NPC83287
0.6829	Remote Similarity	NPC5311
0.6829	Remote Similarity	NPC77299
0.6829	Remote Similarity	NPC480906
0.6818	Remote Similarity	NPC264336
0.6818	Remote Similarity	NPC475629
0.6707	Remote Similarity	NPC196429
0.6705	Remote Similarity	NPC475556
0.6705	Remote Similarity	NPC240070
0.6705	Remote Similarity	NPC311706
0.6548	Remote Similarity	NPC480914
0.6429	Remote Similarity	NPC480915
0.6413	Remote Similarity	NPC146857
0.6413	Remote Similarity	NPC247190
0.6395	Remote Similarity	NPC471353
0.6353	Remote Similarity	NPC10823
0.6292	Remote Similarity	NPC30483
0.6292	Remote Similarity	NPC470897
0.625	Remote Similarity	NPC480907
0.6235	Remote Similarity	NPC34390
0.6222	Remote Similarity	NPC236973
0.6222	Remote Similarity	NPC32177
0.6222	Remote Similarity	NPC469756
0.6222	Remote Similarity	NPC275901
0.6184	Remote Similarity	NPC10232
0.6154	Remote Similarity	NPC480910
0.6154	Remote Similarity	NPC480909
0.6154	Remote Similarity	NPC608063
0.6092	Remote Similarity	NPC180079
0.6047	Remote Similarity	NPC6108
0.6047	Remote Similarity	NPC89514
0.6044	Remote Similarity	NPC27363
0.6044	Remote Similarity	NPC292467
0.6023	Remote Similarity	NPC179412
0.6023	Remote Similarity	NPC471356
0.6022	Remote Similarity	NPC59288
0.6022	Remote Similarity	NPC486143
0.6022	Remote Similarity	NPC486135
0.6022	Remote Similarity	NPC486142
0.6022	Remote Similarity	NPC486137
0.6022	Remote Similarity	NPC486149
0.6	Remote Similarity	NPC471633
0.5978	Remote Similarity	NPC188234
0.5977	Remote Similarity	NPC243196
0.596	Remote Similarity	NPC329675
0.596	Remote Similarity	NPC194716
0.5909	Remote Similarity	NPC146456
0.5843	Remote Similarity	NPC305574
0.5795	Remote Similarity	NPC199428
0.5795	Remote Similarity	NPC109448
0.5795	Remote Similarity	NPC310341
0.5789	Remote Similarity	NPC232785
0.5789	Remote Similarity	NPC486139
0.5729	Remote Similarity	NPC486146
0.5714	Remote Similarity	NPC72260
0.5684	Remote Similarity	NPC125077
0.5657	Remote Similarity	NPC486144
0.5657	Remote Similarity	NPC486145
0.5657	Remote Similarity	NPC486147
0.5657	Remote Similarity	NPC486136
0.5657	Remote Similarity	NPC486148
0.5618	Remote Similarity	NPC604978
0.5579	Remote Similarity	NPC610296
0.5567	Remote Similarity	NPC329986
0.5567	Remote Similarity	NPC140092
0.5556	Remote Similarity	NPC250556
0.5513	Remote Similarity	NPC97487
0.551	Remote Similarity	NPC486138
0.551	Remote Similarity	NPC276838
0.55	Remote Similarity	NPC72772
0.55	Remote Similarity	NPC475590
0.5495	Remote Similarity	NPC471359
0.5495	Remote Similarity	NPC483822
0.5474	Remote Similarity	NPC486130
0.5444	Remote Similarity	NPC84949
0.5444	Remote Similarity	NPC480562
0.5444	Remote Similarity	NPC74945
0.5444	Remote Similarity	NPC31354
0.5444	Remote Similarity	NPC69576
0.5417	Remote Similarity	NPC486127
0.5393	Remote Similarity	NPC484211
0.5392	Remote Similarity	NPC120390
0.5392	Remote Similarity	NPC74259
0.5392	Remote Similarity	NPC475419
0.5347	Remote Similarity	NPC329636
0.534	Remote Similarity	NPC474908
0.534	Remote Similarity	NPC486134
0.534	Remote Similarity	NPC486141
0.5326	Remote Similarity	NPC93883
0.5312	Remote Similarity	NPC471357
0.5312	Remote Similarity	NPC469757
0.5312	Remote Similarity	NPC117702
0.5281	Remote Similarity	NPC473852
0.5269	Remote Similarity	NPC469753
0.5222	Remote Similarity	NPC486129
0.5189	Remote Similarity	NPC474423
0.5165	Remote Similarity	NPC486126
0.5161	Remote Similarity	NPC484202
0.5149	Remote Similarity	NPC486132
0.5149	Remote Similarity	NPC486131
0.5143	Remote Similarity	NPC486150
0.5122	Remote Similarity	NPC222875
0.5122	Remote Similarity	NPC25177
0.5098	Remote Similarity	NPC486128
0.5093	Remote Similarity	NPC286809
0.5051	Remote Similarity	NPC55532
0.5051	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 NPC157376 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6069
0.1-0.2	2928
0.2-0.3	134
0.3-0.4	5
0.4-0.5	7
0.5-0.6	4
0.6-0.7	2
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.84	Intermediate Similarity	NPD7319	Approved
0.6867	Remote Similarity	NPD7327	Approved
0.6867	Remote Similarity	NPD7328	Phase 4
0.5714	Remote Similarity	NPD8294	Phase 4
0.5556	Remote Similarity	NPD7507	Pre-clinical
0.5161	Remote Similarity	NPD7516	Pre-clinical
0.5051	Remote Similarity	NPD8377	Phase 4

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