NPASS Compound

Natural Product: NPC99620

Natural Product ID	NPC99620
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S,3R,4R,5R,6R)-3,4,5,6-Tetrahydro-2-Methyl-6-(Digitoxigenoxy)-2H-Pyran-3,4,5-Triol
IUPAC Name	3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
Synonyms	alpha-L-rhamnose
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1651648
PubChem CID	12308635
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 86 0 0 0 0 0 0 0 0999 V2000 7.3921 0.7461 -2.2833 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5012 0.0926 -1.2255 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3928 -0.4364 -0.1527 C 0 0 1 0 0 0 0 0 0 0 0 0 7.2644 0.5102 1.0449 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8070 0.3647 1.5003 C 0 0 2 0 0 0 0 0 0 0 0 0 4.9116 0.7301 0.3376 C 0 0 1 0 0 0 0 0 0 0 0 0 5.6139 1.0579 -0.8010 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9682 -0.2711 0.1304 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6727 0.1825 0.3733 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8268 0.1395 -0.8856 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0421 -1.1321 -0.8766 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0108 -1.1897 0.2332 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1984 -2.6870 0.5102 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5220 -0.5662 1.4654 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1301 0.8206 1.7667 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1462 1.2928 1.1104 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0175 0.0715 0.7778 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2809 -0.6430 -0.2954 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1046 -1.7713 -0.8566 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3508 -1.1729 -1.4069 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2122 -0.5195 -0.3281 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8483 -1.6526 0.4077 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2275 0.2801 -1.0635 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4791 1.5817 -1.3976 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5990 1.7756 -0.1848 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4223 0.4444 0.5058 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0699 0.5427 1.7354 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5192 0.5608 -0.4646 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0569 0.2995 0.6974 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4387 0.8273 0.7832 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2291 0.7476 1.7552 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6938 1.4233 -0.4067 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5996 1.3194 -1.2296 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0530 -0.6362 1.4550 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6373 1.1916 2.5856 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4841 1.7974 0.5480 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0185 -1.7189 0.1703 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6228 0.0608 -3.1036 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3123 1.1479 -1.8520 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8631 1.6236 -2.7563 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0076 -0.7579 -1.7381 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4770 -0.4146 -0.4337 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9522 0.2421 1.8473 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6706 -0.7133 1.7265 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3517 1.6365 0.6474 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7271 1.2577 0.6800 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1652 1.0066 -0.9961 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4674 0.1177 -1.8003 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7802 -1.9631 -0.6752 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5978 -1.3848 -1.8614 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4136 -3.2401 -0.4017 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9007 -2.8379 1.3394 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8000 -3.0530 0.8768 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2364 -1.2049 2.3554 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0328 0.9596 2.8775 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9092 1.5962 1.5275 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8393 1.7035 0.1160 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6680 2.0136 1.7443 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9310 -0.5716 1.7062 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0576 0.0451 -1.1380 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5472 -2.1978 -1.7430 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3137 -2.5568 -0.1100 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9626 -1.9526 -1.8991 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0883 -0.4243 -2.1764 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8000 -1.5501 1.5260 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9039 -1.8510 0.1360 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3278 -2.6272 0.1497 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4219 -0.1476 -2.1039 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1613 2.4108 -1.5891 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8452 1.4324 -2.2878 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1287 2.5273 0.4596 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6840 2.2501 -0.5225 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6430 -0.0958 2.3592 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6557 -0.2051 1.5520 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1971 2.2907 -1.5883 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8918 0.7156 -2.1391 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3306 -1.7072 1.3916 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4003 -0.3038 2.4756 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8708 1.8208 2.4833 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7533 2.4208 0.7531 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3654 -1.9224 1.0772 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 12 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 1 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 1 23 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 14 34 1 0 5 35 1 0 4 36 1 0 3 37 1 0 7 2 1 0 34 9 1 0 18 12 1 0 26 21 1 0 33 28 1 0 26 17 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 6 3 42 1 6 4 43 1 1 5 44 1 1 6 45 1 1 9 46 1 1 10 47 1 0 10 48 1 0 11 49 1 0 11 50 1 0 13 51 1 0 13 52 1 0 13 53 1 0 14 54 1 1 15 55 1 0 15 56 1 0 16 57 1 0 16 58 1 0 17 59 1 1 18 60 1 6 19 61 1 0 19 62 1 0 20 63 1 0 20 64 1 0 22 65 1 0 22 66 1 0 22 67 1 0 23 68 1 6 24 69 1 0 24 70 1 0 25 71 1 0 25 72 1 0 27 73 1 0 29 74 1 0 33 75 1 0 33 76 1 0 34 77 1 0 34 78 1 0 35 79 1 0 36 80 1 0 37 81 1 0 M END

Standard InCHIKey	WQMLFJWIKARBFW-BKKMTDGVSA-N
Standard InCHI	InChI=1S/C29H44O8/c1-15-23(31)24(32)25(33)26(36-15)37-18-6-9-27(2)17(13-18)4-5-21-20(27)7-10-28(3)19(8-11-29(21,28)34)16-12-22(30)35-14-16/h12,15,17-21,23-26,31-34H,4-11,13-14H2,1-3H3/t15-,17+,18-,19+,20-,21+,23-,24+,25+,26-,27-,28+,29-/m0/s1
SMILES	C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)O[C@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@H](CC[C@]32O)C2=CC(=O)OC2)C1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	520.3	Volume:	523.85 ? Van der Waals volume.
Dense:	0.993	LogP:	2.213 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.703 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.099 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	32.0
TPSA:	125.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.33	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.016	Fsp³:	0.897
MCE-18:	110.618 ? 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:	0.821	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.026 ? 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:	0.152	Promiscuous compounds:	0.227

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.839	MDCK Permeability:	-5.12
Pgp-inhibitor:	0.002	Pgp-substrate:	0.897
PAMPA:	0.99 ? 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):	0.092
20% Bioavailability (F20%):	0.435	30% Bioavailability (F30%):	0.774
50% Bioavailability (F50%):	0.936

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.153	MRP1:	0.425
Plasma Protein Binding (PPB):	75.561%	Volume Distribution (VD):	-0.449
Fu:	22.523% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.988	BCRP inhibitor:	0.203
BSEP inhibitor:	0.131

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.696	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.961	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.034
HLM stability:	0.047 ? 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):

2.461

Half-life (T1/2):

3.701

ADMET: Toxicity

hERG Blockers:	0.12	hERG Blockers (10um):	0.646
Human Hepatotoxicity (H-HT):	0.683	Drug-induced Liver Injury (DILI):	0.936
AMES Toxicity:	0.83	Rat Oral Acute Toxicity:	0.931
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	1.0
Carcinogencity:	0.831	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.977
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.754
Hematotoxicity:	0.681	Drug-induced Nephrotoxicity:	0.992
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.767
A549 Cytotoxicity:	0.25	Hek293 Cytotoxicity:	0.943
BCF:	0.767 ? 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:	3.285 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.648 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.99 ? 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
NPO32604	asclepias fructicosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3981544]

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	6
GI50	63
Activity	26
Ratio IC50	1
EC50	1
CC50	2
Ratio CC50/EC50	1
Relative ionotropic activity	3

Activity Type	# Activity
Cell line	93
Organism	4
Protein complex	2
Non-molecular	3
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2890	Protein complex	Sodium/potassium-transporting ATPase	Homo sapiens	IC50	=	4.79	nM	PMID[21667925]
NPT2890	Protein complex	Sodium/potassium-transporting ATPase	Homo sapiens	IC50	=	6.79	nM	PMID[25237727]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	46.7	nM	PMID[20000576]
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	<	10.0	nM	DrugMatrix in vitro pharmacology data
NPT116	Cell line	HL-60	Homo sapiens	GI50	<	10.0	nM	DrugMatrix in vitro pharmacology data
NPT111	Cell line	K562	Homo sapiens	GI50	<	10.0	nM	DrugMatrix in vitro pharmacology data
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	<	10.0	nM	DrugMatrix in vitro pharmacology data
NPT385	Cell line	SR	Homo sapiens	GI50	<	10.0	nM	DrugMatrix in vitro pharmacology data
NPT81	Cell line	A549	Homo sapiens	GI50	<	10.0	nM	DrugMatrix in vitro pharmacology data
NPT394	Cell line	EKVX	Homo sapiens	GI50	<	10.0	nM	DrugMatrix in vitro pharmacology data
NPT379	Cell line	HOP-62	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT372	Cell line	HOP-92	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	<	10.0	nM	PMID[18625769]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	<	10.0	nM	PMID[20585113]
NPT407	Cell line	COLO 205	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT393	Cell line	HCT-116	Homo sapiens	GI50	<	10.0	nM	PMID[18955526]
NPT148	Cell line	HCT-15	Homo sapiens	GI50	<	10.0	nM	PMID[11549443]
NPT139	Cell line	HT-29	Homo sapiens	GI50	<	10.0	nM	PMID[16499326]
NPT386	Cell line	KM12	Homo sapiens	GI50	<	10.0	nM	PMID[11549443]
NPT323	Cell line	SW-620	Homo sapiens	GI50	<	10.0	nM	PMID[11549443]
NPT395	Cell line	SF-268	Homo sapiens	GI50	<	10.0	nM	PMID[23210623]
NPT399	Cell line	SF-295	Homo sapiens	GI50	<	10.0	nM	PMID[23210623]
NPT374	Cell line	SF-539	Homo sapiens	GI50	<	10.0	nM	PMID[23210623]
NPT383	Cell line	SNB-19	Homo sapiens	GI50	<	10.0	nM	PMID[23210623]
NPT392	Cell line	SNB-75	Homo sapiens	GI50	<	10.0	nM	PMID[18052327]
NPT380	Cell line	U-251	Homo sapiens	GI50	<	10.0	nM	PMID[18052327]
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	<	10.0	nM	PMID[21131198]
NPT387	Cell line	M14	Homo sapiens	GI50	<	10.0	nM	PMID[10924166]
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	<	10.0	nM	PMID[21131198]
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	<	10.0	nM	PMID[21131198]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	<	10.0	nM	PMID[10924166]
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	<	10.0	nM	PMID[10924166]
NPT403	Cell line	UACC-257	Homo sapiens	GI50	<	10.0	nM	PMID[10924166]
NPT398	Cell line	UACC-62	Homo sapiens	GI50	<	10.0	nM	PMID[10924166]
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	<	10.0	nM	PMID[10924166]
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	<	10.0	nM	PMID[10924166]
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0154-3]
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0154-3]
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0154-3]
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0178-8]
NPT401	Cell line	786-0	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0089-8]
NPT376	Cell line	A498	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0089-8]
NPT369	Cell line	ACHN	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0089-8]
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0154-3]
NPT406	Cell line	RXF 393	Homo sapiens	GI50	<	10.0	nM	PMID[24571273]
NPT368	Cell line	SN12C	Homo sapiens	GI50	<	10.0	nM	DOI[10.1007/s00044-012-0178-8]
NPT384	Cell line	TK-10	Homo sapiens	GI50	<	10.0	nM	PMID[12398531]
NPT371	Cell line	UO-31	Homo sapiens	GI50	<	10.0	nM	PMID[12398531]
NPT306	Cell line	PC-3	Homo sapiens	GI50	<	10.0	nM	PMID[22194678]
NPT90	Cell line	DU-145	Homo sapiens	GI50	<	10.0	nM	PMID[12398531]
NPT83	Cell line	MCF7	Homo sapiens	GI50	<	10.0	nM	PMID[17043119]
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	<	10.0	nM	PMID[22506638]
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	<	10.0	nM	PMID[22506638]
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	<	10.0	nM	PMID[22506638]
NPT367	Cell line	MDA-N	Homo sapiens	GI50	<	10.0	nM	PMID[9514009]
NPT457	Cell line	BT-549	Homo sapiens	GI50	<	10.0	nM	PMID[22439674]
NPT396	Cell line	T47D	Homo sapiens	GI50	<	10.0	nM	PMID[22439674]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	45.8	%	PMID[26034885]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	=	2.097	nM	PMID[16309311]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	5.46	%	PMID[9677284]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	5.81	%	PMID[9677284]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	6.11	%	PMID[15646539]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	7.16	%	PMID[22871217]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	8.72	%	PMID[21493075]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	11.81	%	PMID[20498315]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	77.81	%	PMID[17822295]
NPT397	Cell line	NCI-H460	Homo sapiens	Ratio IC50	=	4.0	n.a.	PMID[3443856]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	51.71	nM	PMID[23621840]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	100.0	%	PMID[22037378]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	89.5	%	DOI[10.1039/C1MD00240F]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	78.16	%	PMID[23587837]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	48.79	%	PMID[22691179]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	24.53	%	PMID[21741249]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	16.47	%	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	41.6	%	PMID[20218656]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	=	2.0	nM	PMID[24571273]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	52.0	nM	PMID[8450319]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	48.64	%	DrugMatrix in vivo data: Biochemistry
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	47.03	nM	DrugMatrix in vivo data: Biochemistry
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	96.96	%	PMID[18922036]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	60.56	%	PMID[18053715]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	17.04	%	PMID[18053715]
NPT859	Cell line	HFF	Homo sapiens	CC50	=	700.0	nM	PMID[19220033]
NPT859	Cell line	HFF	Homo sapiens	CC50	=	2000.0	nM	DrugMatrix in vivo data: Pathology
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	1.0	nM	PMID[21643465]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	<	10.0	nM	PMID[21643465]
NPT1750	Organism	Human herpesvirus 5	Human herpesvirus 5	EC50	=	4.8	nM	PMID[17665951]
NPT2	Others	Unspecified	n.a.	Ratio CC50/EC50	=	139.0	n.a.	PMID[15267244]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT938	Organism	Cavia porcellus	Cavia porcellus	Relative ionotropic activity	=	9.0	n.a.	PMID[3981544]
NPT938	Organism	Cavia porcellus	Cavia porcellus	Relative ionotropic activity	=	3.0	n.a.	PMID[3981544]
NPT938	Organism	Cavia porcellus	Cavia porcellus	Relative ionotropic activity	=	22.0	n.a.	PMID[3981544]

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 NPC99620 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	13422
0.1-0.2	29875
0.2-0.3	5712
0.3-0.4	604
0.4-0.5	56
0.5-0.6	70
0.6-0.7	66
0.7-0.8	2
0.8-0.85	5
0.85-0.9	4
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8889	High Similarity	NPC5311
0.863	High Similarity	NPC469750
0.8514	High Similarity	NPC76572
0.8514	High Similarity	NPC193382
0.8108	Intermediate Similarity	NPC471633
0.8101	Intermediate Similarity	NPC30483
0.8101	Intermediate Similarity	NPC470897
0.8	Intermediate Similarity	NPC236973
0.8	Intermediate Similarity	NPC196429
0.7792	Intermediate Similarity	NPC199428
0.7792	Intermediate Similarity	NPC109448
0.7792	Intermediate Similarity	NPC310341
0.7778	Intermediate Similarity	NPC292467
0.7711	Intermediate Similarity	NPC486143
0.7711	Intermediate Similarity	NPC486142
0.7711	Intermediate Similarity	NPC486149
0.7683	Intermediate Similarity	NPC240070
0.7662	Intermediate Similarity	NPC77299
0.7662	Intermediate Similarity	NPC480906
0.7632	Intermediate Similarity	NPC99728
0.7632	Intermediate Similarity	NPC87250
0.7632	Intermediate Similarity	NPC244402
0.7632	Intermediate Similarity	NPC50305
0.7625	Intermediate Similarity	NPC72260
0.7564	Intermediate Similarity	NPC480914
0.7436	Intermediate Similarity	NPC157376
0.7436	Intermediate Similarity	NPC17896
0.7436	Intermediate Similarity	NPC469755
0.7436	Intermediate Similarity	NPC284406
0.7436	Intermediate Similarity	NPC197707
0.7436	Intermediate Similarity	NPC251866
0.7436	Intermediate Similarity	NPC142066
0.7436	Intermediate Similarity	NPC480915
0.7436	Intermediate Similarity	NPC603972
0.7342	Intermediate Similarity	NPC84949
0.7342	Intermediate Similarity	NPC480562
0.7342	Intermediate Similarity	NPC74945
0.7342	Intermediate Similarity	NPC31354
0.7342	Intermediate Similarity	NPC69576
0.7326	Intermediate Similarity	NPC486146
0.7195	Intermediate Similarity	NPC480907
0.7191	Intermediate Similarity	NPC486144
0.7191	Intermediate Similarity	NPC486145
0.7191	Intermediate Similarity	NPC486147
0.7191	Intermediate Similarity	NPC486148
0.716	Intermediate Similarity	NPC179412
0.716	Intermediate Similarity	NPC471356
0.716	Intermediate Similarity	NPC471353
0.7	Intermediate Similarity	NPC475590
0.6951	Remote Similarity	NPC93883
0.6941	Remote Similarity	NPC32177
0.6941	Remote Similarity	NPC469756
0.6941	Remote Similarity	NPC275901
0.686	Remote Similarity	NPC188234
0.686	Remote Similarity	NPC480910
0.686	Remote Similarity	NPC480909
0.6848	Remote Similarity	NPC120390
0.6848	Remote Similarity	NPC74259
0.6848	Remote Similarity	NPC475419
0.6774	Remote Similarity	NPC474908
0.6774	Remote Similarity	NPC486134
0.6774	Remote Similarity	NPC486141
0.6747	Remote Similarity	NPC484202
0.6705	Remote Similarity	NPC55532
0.6705	Remote Similarity	NPC486135
0.6705	Remote Similarity	NPC486137
0.6667	Remote Similarity	NPC84987
0.6667	Remote Similarity	NPC309034
0.6629	Remote Similarity	NPC232785
0.6629	Remote Similarity	NPC486139
0.6627	Remote Similarity	NPC250556
0.6598	Remote Similarity	NPC286809
0.6562	Remote Similarity	NPC474423
0.6552	Remote Similarity	NPC27363
0.6548	Remote Similarity	NPC305574
0.6517	Remote Similarity	NPC125077
0.6429	Remote Similarity	NPC77319
0.6429	Remote Similarity	NPC471351
0.6429	Remote Similarity	NPC471355
0.6404	Remote Similarity	NPC231518
0.6404	Remote Similarity	NPC488944
0.6386	Remote Similarity	NPC479356
0.6386	Remote Similarity	NPC479355
0.6374	Remote Similarity	NPC329986
0.6374	Remote Similarity	NPC140092
0.6341	Remote Similarity	NPC473852
0.6333	Remote Similarity	NPC208193
0.6322	Remote Similarity	NPC173555
0.6304	Remote Similarity	NPC486138
0.6304	Remote Similarity	NPC276838
0.6279	Remote Similarity	NPC193893
0.6277	Remote Similarity	NPC486136
0.622	Remote Similarity	NPC158344
0.6216	Remote Similarity	NPC268829
0.6216	Remote Similarity	NPC295110
0.6163	Remote Similarity	NPC483822
0.6163	Remote Similarity	NPC9499
0.6163	Remote Similarity	NPC471360
0.6163	Remote Similarity	NPC469751
0.6163	Remote Similarity	NPC471361
0.6163	Remote Similarity	NPC86159
0.6163	Remote Similarity	NPC469752
0.6163	Remote Similarity	NPC469754
0.6163	Remote Similarity	NPC70542
0.6092	Remote Similarity	NPC471354
0.6092	Remote Similarity	NPC27507
0.6087	Remote Similarity	NPC469749
0.6071	Remote Similarity	NPC219085
0.6024	Remote Similarity	NPC474418
0.6	Remote Similarity	NPC479360
0.6	Remote Similarity	NPC479359
0.6	Remote Similarity	NPC488943
0.6	Remote Similarity	NPC99080
0.6	Remote Similarity	NPC40749
0.6	Remote Similarity	NPC488942
0.5955	Remote Similarity	NPC5883
0.5934	Remote Similarity	NPC32793
0.5934	Remote Similarity	NPC116075
0.5895	Remote Similarity	NPC475219
0.587	Remote Similarity	NPC475629
0.5862	Remote Similarity	NPC83287
0.5859	Remote Similarity	NPC486150
0.5833	Remote Similarity	NPC488938
0.5833	Remote Similarity	NPC488937
0.5761	Remote Similarity	NPC475556
0.5761	Remote Similarity	NPC479353
0.5761	Remote Similarity	NPC479354
0.5761	Remote Similarity	NPC311706
0.5761	Remote Similarity	NPC486130
0.5758	Remote Similarity	NPC117445
0.5758	Remote Similarity	NPC308262
0.5699	Remote Similarity	NPC488941
0.5699	Remote Similarity	NPC488940
0.5699	Remote Similarity	NPC486127
0.5698	Remote Similarity	NPC486129
0.5644	Remote Similarity	NPC488945
0.5644	Remote Similarity	NPC488946
0.5632	Remote Similarity	NPC486126
0.5604	Remote Similarity	NPC103534
0.5604	Remote Similarity	NPC44899
0.5604	Remote Similarity	NPC304260
0.5604	Remote Similarity	NPC29639
0.5581	Remote Similarity	NPC479351
0.5581	Remote Similarity	NPC479352
0.5568	Remote Similarity	NPC10823
0.5568	Remote Similarity	NPC480908
0.5521	Remote Similarity	NPC146857
0.5521	Remote Similarity	NPC247190
0.5455	Remote Similarity	NPC34390
0.5444	Remote Similarity	NPC277374
0.5443	Remote Similarity	NPC222875
0.5443	Remote Similarity	NPC25177
0.5437	Remote Similarity	NPC488947
0.5435	Remote Similarity	NPC488935
0.5435	Remote Similarity	NPC488936
0.5408	Remote Similarity	NPC476221
0.5408	Remote Similarity	NPC477709
0.5408	Remote Similarity	NPC479357
0.5408	Remote Similarity	NPC486132
0.5408	Remote Similarity	NPC486131
0.5393	Remote Similarity	NPC243196
0.5393	Remote Similarity	NPC152615
0.5393	Remote Similarity	NPC604978
0.5385	Remote Similarity	NPC187302
0.5368	Remote Similarity	NPC264336
0.5368	Remote Similarity	NPC610296
0.5361	Remote Similarity	NPC488939
0.5354	Remote Similarity	NPC486128
0.5333	Remote Similarity	NPC146456
0.5333	Remote Similarity	NPC88668
0.5333	Remote Similarity	NPC180079
0.5316	Remote Similarity	NPC196931
0.5316	Remote Similarity	NPC480913
0.5281	Remote Similarity	NPC6108
0.5281	Remote Similarity	NPC89514
0.5281	Remote Similarity	NPC477580
0.5263	Remote Similarity	NPC608063
0.5169	Remote Similarity	NPC484211
0.5155	Remote Similarity	NPC59288
0.5146	Remote Similarity	NPC486140
0.5146	Remote Similarity	NPC329675
0.5146	Remote Similarity	NPC194716
0.5104	Remote Similarity	NPC486151
0.5096	Remote Similarity	NPC486133
0.5063	Remote Similarity	NPC97487

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC99620 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5739
0.1-0.2	3224
0.2-0.3	167
0.3-0.4	4
0.4-0.5	3
0.5-0.6	7
0.6-0.7	4
0.7-0.8	2
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
0.7625	Intermediate Similarity	NPD8294	Phase 4
0.7436	Intermediate Similarity	NPD7319	Approved
0.6705	Remote Similarity	NPD8377	Phase 4
0.6627	Remote Similarity	NPD7507	Pre-clinical
0.6404	Remote Similarity	NPD8033	Approved
0.6322	Remote Similarity	NPD8296	Phase 4
0.5862	Remote Similarity	NPD7327	Approved
0.5862	Remote Similarity	NPD7328	Phase 4
0.5862	Remote Similarity	NPD8335	Phase 4
0.5795	Remote Similarity	NPD8380	Approved
0.5579	Remote Similarity	NPD8378	Pre-clinical
0.5579	Remote Similarity	NPD8379	Approved
0.5238	Remote Similarity	NPD6940	Discontinued

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