NPASS Compound

Natural Product: NPC251866

Natural Product ID	NPC251866
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Convallatoxin
IUPAC Name	(3S,5S,8R,9S,10S,13R,14S,17R)-5,14-dihydroxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-3-[(2R,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]phenanthrene-10-carbaldehyde
Synonyms	Convallatoxin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL399336
PubChem CID	441852
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 0.4690 -0.8842 2.7358 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0349 -1.3589 1.7152 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0960 -0.6579 0.4217 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7557 -1.4429 -0.5760 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1094 -1.6348 0.0309 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7833 -0.2857 0.1639 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9444 0.7297 0.8418 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4906 0.7161 0.5043 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1467 1.3615 1.5935 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3031 1.4853 -0.7790 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9718 1.1864 -1.4932 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9985 0.6886 -0.5329 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5452 -0.6233 0.0258 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4463 -1.0560 1.1216 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7920 -0.4933 1.1754 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3413 0.2469 0.0086 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3716 0.5548 -1.0771 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7116 1.8007 -1.6492 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5990 -0.4689 -2.1121 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1462 -0.4501 -2.1630 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4186 -0.5567 -0.6785 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.7909 -0.2139 -0.3256 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7155 0.2317 -1.1714 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9582 0.4719 -0.4942 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0360 0.8950 -0.9948 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7633 0.1509 0.8345 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4542 -0.3039 0.9984 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9607 1.5648 0.4507 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9310 -0.4954 0.9395 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0949 -0.2782 0.1924 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8329 -1.4429 0.2412 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1012 -1.3181 -0.2876 C 0 0 1 0 0 0 0 0 0 0 0 0 7.0804 -1.2164 -1.8048 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9094 -0.2248 0.3294 C 0 0 1 0 0 0 0 0 0 0 0 0 7.0820 0.3633 1.4712 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8073 0.9028 0.8158 C 0 0 1 0 0 0 0 0 0 0 0 0 6.2180 1.8350 -0.1342 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8304 1.4020 2.0113 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0990 -0.6828 0.8966 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2869 -2.4093 1.7741 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2916 -2.4452 -0.7091 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8179 -0.9643 -1.5517 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9903 -2.0549 1.0387 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7231 -2.2458 -0.6516 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0662 0.0112 -0.8819 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0738 0.6161 1.9466 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3299 1.7455 0.6070 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3852 2.1787 1.8170 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4369 2.5672 -0.5389 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1634 1.2325 -1.4505 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3547 2.1696 -1.8979 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8578 0.5380 -2.3838 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0744 1.4666 0.2854 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6383 -1.3683 -0.8189 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8885 -0.8662 2.0900 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4795 -2.1876 1.0902 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8692 0.1852 2.0677 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5256 -1.3178 1.4286 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3201 1.9065 -2.5517 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3534 -1.5026 -1.8784 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2393 -0.1399 -3.1123 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5374 -1.3592 -2.6424 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5237 0.4679 -2.6120 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2555 -1.6385 -0.3838 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5867 0.4060 -2.2491 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4542 -1.3879 1.2948 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8871 0.2844 1.7486 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9721 1.6626 0.0333 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3918 2.4409 0.0151 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9721 1.6696 1.5591 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8190 0.0084 -0.8397 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6327 -2.2875 -0.0572 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9901 -0.1273 -2.0392 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0545 -1.5477 -2.2359 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2837 -1.8122 -2.2524 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1211 0.5680 -0.4213 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8746 -0.4392 2.1850 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2246 1.3844 1.6049 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7572 1.7581 -0.9886 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3229 2.2386 2.1254 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4967 0.0968 1.3701 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 3 2 1 1 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 1 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 1 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 2 40 1 0 4 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 6 45 1 6 7 46 1 0 7 47 1 0 9 48 1 0 10 49 1 0 10 50 1 0 11 51 1 0 11 52 1 0 12 53 1 1 13 54 1 6 14 55 1 0 14 56 1 0 15 57 1 0 15 58 1 0 18 59 1 0 19 60 1 0 19 61 1 0 20 62 1 0 20 63 1 0 21 64 1 1 23 65 1 0 27 66 1 0 27 67 1 0 28 68 1 0 28 69 1 0 28 70 1 0 30 71 1 6 32 72 1 6 33 73 1 0 33 74 1 0 33 75 1 0 34 76 1 6 35 77 1 1 36 78 1 1 37 79 1 0 38 80 1 0 39 81 1 0 M END

Standard InCHIKey	HULMNSIAKWANQO-JQKSAQOKSA-N
Standard InCHI	InChI=1S/C29H42O10/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/h11,14-15,17-20,22-25,32-36H,3-10,12-13H2,1-2H3/t15-,17-,18+,19-,20+,22-,23+,24+,25-,26+,27-,28-,29-/m0/s1
SMILES	O=C[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:	550.28	Volume:	538.794 ? Van der Waals volume.
Dense:	1.021	LogP:	0.72 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.383 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.167 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	33.0
TPSA:	162.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.192	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.311	Fsp³:	0.862
MCE-18:	116.926 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.793	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.144	Promiscuous compounds:	0.444

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.584	MDCK Permeability:	-5.298
Pgp-inhibitor:	0.0	Pgp-substrate:	0.994
PAMPA:	0.999 ? 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):	0.122
20% Bioavailability (F20%):	0.678	30% Bioavailability (F30%):	0.894
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.204	MRP1:	0.265
Plasma Protein Binding (PPB):	58.787%	Volume Distribution (VD):	-0.541
Fu:	42.013% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.038
BSEP inhibitor:	0.021

ADMET: Metabolism

CYP1A2-inhibitor:	0.513	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.013	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.008	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.404
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.28
HLM stability:	0.005 ? 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):

1.458

Half-life (T1/2):

4.482

ADMET: Toxicity

hERG Blockers:	0.137	hERG Blockers (10um):	0.709
Human Hepatotoxicity (H-HT):	0.856	Drug-induced Liver Injury (DILI):	0.56
AMES Toxicity:	0.759	Rat Oral Acute Toxicity:	0.956
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.925	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.977
Drug-induced Neurotoxicity:	0.005	Ototoxicity:	0.72
Hematotoxicity:	0.286	Drug-induced Nephrotoxicity:	0.989
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.814
A549 Cytotoxicity:	0.47	Hek293 Cytotoxicity:	0.982
BCF:	0.568 ? 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:	3.276 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.759 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.049 ? 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
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	flower	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1021/np8006342]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	twig	n.a.	DOI[10.1021/np8006342]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[17268112]
NPO587	Saussurea stella	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17844995]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	twig	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	flower	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	leaf	n.a.	PMID[19405508]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	fruit	n.a.	PMID[19405508]
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]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[6893493]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[6893493]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
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]
NPO587	Saussurea stella	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27978	Crossosoma bigelovii	Species	Crossosomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO157	Convallaria majalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
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
Potency	4
Inhibition	3
IC50	7
Activity	9
EC50	1
Ratio	2
GI50	58
ED50	10
Survival	3

Activity Type	# Activity
Cell line	72
Individual protein	3
Organism	2
Non-molecular	14
Protein family	3
Others	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT72	Individual protein	Solute carrier organic anion transporter family member 1B3	Homo sapiens	Inhibition	=	95.81	%	PMID[23571415]
NPT73	Individual protein	Solute carrier organic anion transporter family member 1B1	Homo sapiens	Inhibition	=	102.27	%	PMID[23571415]
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	223.9	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	=	50.0	nM	PMID[17844995]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	0.39	n.a.	PMID[19894733]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	0.04	n.a.	PMID[19894733]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	<	40.0	nM	PMID[19894733]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	550.0	nM	PMID[19894733]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	0.00869	nM	PubChem BioAssay data set
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	0.04295	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	0.009931	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	0.009727	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	0.0342	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	0.04831	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	0.006653	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	0.01832	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	0.02046	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	0.03707	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	0.05741	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	0.0492	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	0.008913	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	0.006012	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	0.01054	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	0.05585	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	0.01262	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	0.04236	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	0.02938	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	17.82	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	0.13	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	0.03926	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	0.02877	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	0.009931	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	0.08395	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	14.59	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	0.04446	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	0.02884	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	0.007278	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	0.02931	nM	PubChem BioAssay data set
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	0.01324	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	0.07096	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	0.04295	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	0.04688	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	0.01213	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	0.009506	nM	PubChem BioAssay data set
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	0.02624	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	0.04375	nM	PubChem BioAssay data set
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	0.05623	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	0.008472	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	0.05848	nM	PubChem BioAssay data set
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	0.04227	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	0.0123	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	0.02729	nM	PubChem BioAssay data set
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	0.06668	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	0.00879	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	0.05346	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	0.06397	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	0.04775	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	0.09354	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	0.01667	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	0.0013	ug ml-1	PMID[24582402]
NPT308	Cell line	CAKI-1	Homo sapiens	ED50	=	0.0031	ug ml-1	PMID[24582402]
NPT309	Cell line	1A9	Homo sapiens	ED50	=	0.03	ug ml-1	PMID[24582402]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	0.094	ug ml-1	PMID[24582402]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.0065	ug ml-1	PMID[24582402]
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.0027	ug ml-1	PMID[24582402]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.014	ug ml-1	PMID[24582402]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	20000.0	nM	DOI[10.6019/CHEMBL4651402]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	19952.62	nM	DOI[10.6019/CHEMBL4651402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	16.0	nM	PMID[17844995]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.03	n.a.	PMID[19894733]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	<	40.0	nM	PMID[19894733]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.1	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.125	uM	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	467.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	300.0	%	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	10.0	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Ratio	=	8.0	n.a.	PMID[20553004]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	82.1	%	PMID[24033101]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.0014	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.014	ug ml-1	PMID[24582402]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.013	ug ml-1	PMID[24582402]
NPT21802	Protein family	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	Activity	=	77.0	%	PMID[19405508]
NPT21802	Protein family	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	Activity	=	50.0	%	PMID[19405508]
NPT21802	Protein family	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	EC50	=	20.0	nM	PMID[19405508]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	112.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	100.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	631.0	nM	PubChem BioAssay data set

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT393	Cell line	HCT-116	Homo sapiens	Survival	=	3.0	%	PMID[19894733]
NPT139	Cell line	HT-29	Homo sapiens	Survival	=	20.0	%	PMID[19894733]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Survival	=	1.0	%	PMID[19894733]

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
-	Mus musculus	LD50	>	2000.0	mg/kg	ToxVal
-	Cavia porcellus	LD50	>	50.0	mg/kg	ToxVal

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 NPC251866 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	15723
0.1-0.2	28744
0.2-0.3	4828
0.3-0.4	344
0.4-0.5	70
0.5-0.6	71
0.6-0.7	33
0.7-0.8	0
0.8-0.85	13
0.85-0.9	4
0.9-0.95	0
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC17896
1.0	High Similarity	NPC469755
1.0	High Similarity	NPC284406
1.0	High Similarity	NPC197707
0.863	High Similarity	NPC99728
0.863	High Similarity	NPC87250
0.863	High Similarity	NPC244402
0.863	High Similarity	NPC50305
0.84	Intermediate Similarity	NPC157376
0.84	Intermediate Similarity	NPC142066
0.84	Intermediate Similarity	NPC603972
0.8267	Intermediate Similarity	NPC219085
0.8077	Intermediate Similarity	NPC9499
0.8077	Intermediate Similarity	NPC471360
0.8077	Intermediate Similarity	NPC469751
0.8077	Intermediate Similarity	NPC471361
0.8077	Intermediate Similarity	NPC86159
0.8077	Intermediate Similarity	NPC469752
0.8077	Intermediate Similarity	NPC469754
0.8077	Intermediate Similarity	NPC70542
0.8072	Intermediate Similarity	NPC469749
0.7927	Intermediate Similarity	NPC32793
0.7927	Intermediate Similarity	NPC116075
0.7692	Intermediate Similarity	NPC469750
0.7595	Intermediate Similarity	NPC10823
0.7564	Intermediate Similarity	NPC84987
0.7564	Intermediate Similarity	NPC309034
0.7436	Intermediate Similarity	NPC99620
0.7356	Intermediate Similarity	NPC146857
0.7356	Intermediate Similarity	NPC247190
0.7284	Intermediate Similarity	NPC77319
0.7284	Intermediate Similarity	NPC471351
0.7284	Intermediate Similarity	NPC180079
0.7284	Intermediate Similarity	NPC471355
0.725	Intermediate Similarity	NPC6108
0.725	Intermediate Similarity	NPC89514
0.716	Intermediate Similarity	NPC76572
0.716	Intermediate Similarity	NPC193382
0.7093	Intermediate Similarity	NPC608063
0.7089	Intermediate Similarity	NPC158344
0.6905	Remote Similarity	NPC471354
0.6905	Remote Similarity	NPC27507
0.6875	Remote Similarity	NPC474418
0.6829	Remote Similarity	NPC480915
0.6809	Remote Similarity	NPC329675
0.6809	Remote Similarity	NPC194716
0.6747	Remote Similarity	NPC480914
0.6742	Remote Similarity	NPC59288
0.6707	Remote Similarity	NPC196429
0.6629	Remote Similarity	NPC475629
0.6627	Remote Similarity	NPC5311
0.6517	Remote Similarity	NPC475556
0.6517	Remote Similarity	NPC240070
0.6517	Remote Similarity	NPC311706
0.6471	Remote Similarity	NPC83287
0.6429	Remote Similarity	NPC77299
0.6429	Remote Similarity	NPC480906
0.6395	Remote Similarity	NPC471359
0.6395	Remote Similarity	NPC179412
0.6395	Remote Similarity	NPC471356
0.6316	Remote Similarity	NPC329636
0.6316	Remote Similarity	NPC72772
0.6235	Remote Similarity	NPC34390
0.6154	Remote Similarity	NPC188234
0.6136	Remote Similarity	NPC469753
0.6118	Remote Similarity	NPC484211
0.6111	Remote Similarity	NPC30483
0.6111	Remote Similarity	NPC470897
0.6067	Remote Similarity	NPC480907
0.6044	Remote Similarity	NPC236973
0.6044	Remote Similarity	NPC27363
0.6023	Remote Similarity	NPC471353
0.6	Remote Similarity	NPC471633
0.5957	Remote Similarity	NPC232785
0.5957	Remote Similarity	NPC486139
0.5914	Remote Similarity	NPC264336
0.5909	Remote Similarity	NPC250556
0.587	Remote Similarity	NPC32177
0.587	Remote Similarity	NPC292467
0.587	Remote Similarity	NPC469756
0.587	Remote Similarity	NPC275901
0.5851	Remote Similarity	NPC486143
0.5851	Remote Similarity	NPC125077
0.5851	Remote Similarity	NPC486142
0.5851	Remote Similarity	NPC486149
0.5833	Remote Similarity	NPC486138
0.5833	Remote Similarity	NPC276838
0.5806	Remote Similarity	NPC480910
0.5806	Remote Similarity	NPC480909
0.5795	Remote Similarity	NPC199428
0.5795	Remote Similarity	NPC243196
0.5795	Remote Similarity	NPC109448
0.5795	Remote Similarity	NPC310341
0.573	Remote Similarity	NPC146456
0.5729	Remote Similarity	NPC329986
0.5729	Remote Similarity	NPC140092
0.5729	Remote Similarity	NPC486146
0.5714	Remote Similarity	NPC72260
0.5684	Remote Similarity	NPC486135
0.5684	Remote Similarity	NPC486137
0.5618	Remote Similarity	NPC604978
0.5579	Remote Similarity	NPC610296
0.5556	Remote Similarity	NPC484212
0.5513	Remote Similarity	NPC97487
0.5506	Remote Similarity	NPC484210
0.55	Remote Similarity	NPC486144
0.55	Remote Similarity	NPC486145
0.55	Remote Similarity	NPC486147
0.55	Remote Similarity	NPC486148
0.5495	Remote Similarity	NPC93883
0.5495	Remote Similarity	NPC305574
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
0.5437	Remote Similarity	NPC486150
0.5417	Remote Similarity	NPC486127
0.5375	Remote Similarity	NPC10232
0.5368	Remote Similarity	NPC62172
0.5347	Remote Similarity	NPC475590
0.5347	Remote Similarity	NPC486136
0.534	Remote Similarity	NPC486134
0.534	Remote Similarity	NPC486141
0.5333	Remote Similarity	NPC486126
0.5312	Remote Similarity	NPC471357
0.5312	Remote Similarity	NPC469757
0.5312	Remote Similarity	NPC75616
0.5312	Remote Similarity	NPC117702
0.5312	Remote Similarity	NPC486130
0.5281	Remote Similarity	NPC473852
0.5243	Remote Similarity	NPC120390
0.5243	Remote Similarity	NPC74259
0.5243	Remote Similarity	NPC475419
0.5222	Remote Similarity	NPC486129
0.5217	Remote Similarity	NPC88668
0.5192	Remote Similarity	NPC474908
0.5161	Remote Similarity	NPC483822
0.5161	Remote Similarity	NPC484202
0.5161	Remote Similarity	NPC277374
0.5098	Remote Similarity	NPC486128
0.5093	Remote Similarity	NPC286809
0.5051	Remote Similarity	NPC55532
0.5047	Remote Similarity	NPC474423

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC251866 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6152
0.1-0.2	2856
0.2-0.3	123
0.3-0.4	6
0.4-0.5	6
0.5-0.6	4
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD7319	Approved
0.6471	Remote Similarity	NPD7327	Approved
0.6471	Remote Similarity	NPD7328	Phase 4
0.5909	Remote Similarity	NPD7507	Pre-clinical
0.5714	Remote Similarity	NPD8294	Phase 4
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