NPASS Compound

Natural Product: NPC105339

Natural Product ID	NPC105339
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NBMKMJSSZYZNRL-LZLDEQLBSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	23304703
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 105111 0 0 0 0 0 0 0 0999 V2000 -3.5166 4.4727 -2.8951 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4788 3.0947 -2.2808 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5231 2.1893 -2.8545 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2046 0.7887 -2.3038 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1864 0.8702 -0.7924 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1859 1.9174 -0.3159 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4312 3.1483 -0.9111 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9467 1.4215 -0.5567 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1308 1.1931 0.5620 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8934 -0.2530 0.6782 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5502 -0.6708 0.7077 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3991 0.1354 -0.2504 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7262 0.1475 -1.6038 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3820 1.5463 0.2849 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3290 1.7418 1.4443 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7317 1.3100 1.1943 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8572 0.6801 -0.1322 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7945 -0.3983 -0.3326 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0741 -1.6240 0.4544 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4698 -1.8598 0.8727 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5596 -1.1802 0.1276 C 0 0 2 0 0 0 0 0 0 0 0 0 6.1549 -2.1419 -0.8770 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6765 -0.8529 1.1405 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9210 0.6273 1.0121 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3357 1.0542 -0.2886 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1878 0.1182 -0.5078 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1394 -0.0784 -1.8987 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8685 -1.6906 0.9741 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1190 -1.3193 0.6511 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9966 -2.4846 0.5891 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2419 -2.4693 0.3100 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2335 -3.5897 0.8857 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9479 -3.1524 1.2284 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0489 2.1049 0.5815 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0941 -0.3302 -0.1526 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2212 -0.5962 0.6016 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9414 -1.8533 0.1276 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.1054 -2.1078 1.0246 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.3295 -1.0164 2.0417 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0638 -0.5597 2.6979 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9408 -1.1525 4.0992 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1147 -0.8777 4.7968 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9331 -0.7978 1.9459 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0946 0.0210 1.5115 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2613 -2.1626 0.2326 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2858 -1.7741 -1.2108 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9436 0.4706 -2.8038 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0003 -0.6465 -3.6472 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8186 2.5560 -2.5515 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2829 4.4488 -3.9808 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4628 5.0162 -2.7384 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6977 5.0803 -2.4249 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4851 2.6597 -2.6032 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3893 2.1445 -3.9428 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9451 0.0938 -2.6870 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1855 1.3234 -0.5226 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3402 2.0362 0.7714 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7931 1.5080 1.4170 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4322 -0.8974 -0.0788 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3334 -0.6561 1.6456 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5590 -1.7542 0.4875 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8880 -0.4686 1.7681 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4549 -0.2391 -2.3629 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2065 -0.4220 -1.5981 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4599 1.1940 -1.8438 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8025 2.1841 -0.5486 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8568 1.2357 2.3296 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2622 2.8391 1.7040 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0638 0.6833 2.0431 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3760 2.2284 1.2406 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6657 1.4804 -0.9073 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9568 -0.6958 -1.4173 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6823 -2.5121 -0.1279 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4593 -1.6866 1.4004 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6686 -2.9741 0.8240 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6126 -1.6569 1.9784 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2423 -2.1653 -0.9042 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8554 -1.7515 -1.8995 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6450 -3.1297 -0.8368 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3069 -1.0205 2.1920 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4333 1.1896 1.8645 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9910 0.8885 1.1005 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0564 2.1170 -0.3412 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1393 0.9200 -1.0743 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9689 0.8210 -2.2838 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4433 -0.2966 0.4576 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1386 -3.7526 0.8236 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8762 -3.3054 2.3618 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1203 2.6277 1.5785 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2297 2.9713 -0.0993 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9823 0.2123 0.5487 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2103 -2.6939 0.2713 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0390 -3.0911 1.5560 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9710 -1.4860 2.8430 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1325 0.5405 2.8545 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0544 -0.7530 4.6015 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9179 -2.2632 3.9594 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5186 -0.0095 4.4980 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0455 0.8394 2.0290 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2695 -1.3382 -0.3272 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3459 -2.7119 -1.5756 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6511 -0.5018 -4.5158 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9470 -0.8830 -3.9242 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3471 -1.4810 -2.9914 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8695 3.3443 -1.9413 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 6 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 6 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 6 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 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 40 43 1 0 39 44 1 0 38 45 1 0 37 46 1 0 4 47 1 0 47 48 1 0 3 49 1 0 7 2 1 0 34 9 1 0 43 36 1 0 18 12 1 0 26 21 1 0 33 28 1 0 26 17 1 0 1 50 1 0 1 51 1 0 1 52 1 0 2 53 1 6 3 54 1 6 4 55 1 1 5 56 1 1 6 57 1 1 9 58 1 1 10 59 1 0 10 60 1 0 11 61 1 0 11 62 1 0 13 63 1 0 13 64 1 0 13 65 1 0 14 66 1 6 15 67 1 0 15 68 1 0 16 69 1 0 16 70 1 0 17 71 1 0 18 72 1 0 19 73 1 0 19 74 1 0 20 75 1 0 20 76 1 0 22 77 1 0 22 78 1 0 22 79 1 0 23 80 1 0 24 81 1 0 24 82 1 0 25 83 1 0 25 84 1 0 27 85 1 0 29 86 1 0 33 87 1 0 33 88 1 0 34 89 1 0 34 90 1 0 36 91 1 1 37 92 1 6 38 93 1 1 39 94 1 1 40 95 1 1 41 96 1 0 41 97 1 0 42 98 1 0 44 99 1 0 45100 1 0 46101 1 0 48102 1 0 48103 1 0 48104 1 0 49105 1 0 M END

Standard InCHIKey	NBMKMJSSZYZNRL-LZLDEQLBSA-N
Standard InCHI	InChI=1S/C36H56O13/c1-17-26(39)30(44-4)31(49-32-29(42)28(41)27(40)24(15-37)48-32)33(46-17)47-20-7-10-34(2)19(14-20)5-6-23-22(34)8-11-35(3)21(9-12-36(23,35)43)18-13-25(38)45-16-18/h13,17,19-24,26-33,37,39-43H,5-12,14-16H2,1-4H3/t17-,19-,20+,21?,22?,23?,24-,26+,27-,28-,29-,30-,31-,32+,33-,34+,35-,36+/m1/s1
SMILES	C[C@@H]1[C@@H]([C@H]([C@H]([C@H](O1)O[C@H]1CC[C@@]2(C)[C@H](CCC3C2CC[C@]2(C)C(CC[C@]32O)C2=CC(=O)OC2)C1)O[C@H]1[C@@H]([C@@H]([C@@H]([C@@H](CO)O1)O)O)O)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	696.37	Volume:	680.317 ? Van der Waals volume.
Dense:	1.024	LogP:	0.822 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.435 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.02 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	38.0
TPSA:	193.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	6.0	Rings:	7.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.163	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.588	Fsp³:	0.917
MCE-18:	132.145 ? 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:	0.657	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.144	Promiscuous compounds:	0.224

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.95	MDCK Permeability:	-5.209
Pgp-inhibitor:	0.0	Pgp-substrate:	0.941
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):	0.014
20% Bioavailability (F20%):	0.638	30% Bioavailability (F30%):	0.562
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.986
Plasma Protein Binding (PPB):	79.806%	Volume Distribution (VD):	-0.409
Fu:	15.352% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.955
OATP1B3 inhibitor:	0.848	BCRP inhibitor:	0.0
BSEP inhibitor:	0.444

ADMET: Metabolism

CYP1A2-inhibitor:	0.406	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.992	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.014	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.994	CYP3A4-substrate:	0.074
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.463
HLM stability:	0.255 ? 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):

3.543

ADMET: Toxicity

hERG Blockers:	0.049	hERG Blockers (10um):	0.208
Human Hepatotoxicity (H-HT):	0.743	Drug-induced Liver Injury (DILI):	0.333
AMES Toxicity:	0.943	Rat Oral Acute Toxicity:	0.25
Maximum Recommended Daily Dose:	0.746	Skin Sensitization:	1.0
Carcinogencity:	0.609	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.079
Drug-induced Neurotoxicity:	0.014	Ototoxicity:	0.994
Hematotoxicity:	0.314	Drug-induced Nephrotoxicity:	0.845
Genotoxicity:	0.338	RPMI-8226 Immunitoxicity:	0.422
A549 Cytotoxicity:	0.93	Hek293 Cytotoxicity:	0.937
BCF:	0.537 ? 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:	3.349 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.974 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.076 ? 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
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	leaves	Niigata City, Niigata Province, Japan	2000-Nov	PMID[15730243]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	leaves	n.a.	n.a.	PMID[16933868]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17253842]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	stems and twigs	Niigata City, Niigata Province, Japan	2001-NOV	PMID[17595134]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	stems and twigs	n.a.	n.a.	PMID[17595134]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29693393]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	Leaves; Stems	n.a.	n.a.	PMID[9214727]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10021	Nerium oleander	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10021	Nerium oleander	Species	Apocynaceae	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

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

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 NPC105339 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	14770
0.1-0.2	29606
0.2-0.3	4121
0.3-0.4	1087
0.4-0.5	99
0.5-0.6	73
0.6-0.7	77
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8222	Intermediate Similarity	NPC486146
0.8193	Intermediate Similarity	NPC5311
0.8118	Intermediate Similarity	NPC93883
0.7865	Intermediate Similarity	NPC292467
0.7802	Intermediate Similarity	NPC486143
0.7802	Intermediate Similarity	NPC486142
0.7802	Intermediate Similarity	NPC486149
0.7667	Intermediate Similarity	NPC236973
0.7629	Intermediate Similarity	NPC486134
0.7629	Intermediate Similarity	NPC486141
0.7556	Intermediate Similarity	NPC30483
0.7556	Intermediate Similarity	NPC470897
0.7529	Intermediate Similarity	NPC99620
0.732	Intermediate Similarity	NPC486144
0.732	Intermediate Similarity	NPC486145
0.732	Intermediate Similarity	NPC486147
0.732	Intermediate Similarity	NPC486148
0.7188	Intermediate Similarity	NPC486138
0.7188	Intermediate Similarity	NPC276838
0.7172	Intermediate Similarity	NPC120390
0.7159	Intermediate Similarity	NPC77299
0.7159	Intermediate Similarity	NPC480906
0.7079	Intermediate Similarity	NPC480914
0.7021	Intermediate Similarity	NPC240070
0.7	Intermediate Similarity	NPC475419
0.697	Remote Similarity	NPC475590
0.6893	Remote Similarity	NPC474423
0.6889	Remote Similarity	NPC199428
0.6889	Remote Similarity	NPC84949
0.6889	Remote Similarity	NPC109448
0.6889	Remote Similarity	NPC76572
0.6889	Remote Similarity	NPC480562
0.6889	Remote Similarity	NPC74945
0.6889	Remote Similarity	NPC310341
0.6889	Remote Similarity	NPC31354
0.6889	Remote Similarity	NPC193382
0.6889	Remote Similarity	NPC69576
0.6875	Remote Similarity	NPC486135
0.6875	Remote Similarity	NPC486137
0.6832	Remote Similarity	NPC74259
0.6804	Remote Similarity	NPC232785
0.6804	Remote Similarity	NPC486139
0.6774	Remote Similarity	NPC480907
0.6737	Remote Similarity	NPC32177
0.6737	Remote Similarity	NPC469756
0.6737	Remote Similarity	NPC275901
0.67	Remote Similarity	NPC488938
0.67	Remote Similarity	NPC488937
0.6699	Remote Similarity	NPC486150
0.6667	Remote Similarity	NPC188234
0.6667	Remote Similarity	NPC480910
0.6667	Remote Similarity	NPC480909
0.6602	Remote Similarity	NPC474908
0.6598	Remote Similarity	NPC231518
0.6598	Remote Similarity	NPC488944
0.6593	Remote Similarity	NPC469750
0.6566	Remote Similarity	NPC329986
0.6566	Remote Similarity	NPC140092
0.6566	Remote Similarity	NPC247190
0.6556	Remote Similarity	NPC471633
0.6531	Remote Similarity	NPC125077
0.6526	Remote Similarity	NPC488935
0.6526	Remote Similarity	NPC488936
0.6484	Remote Similarity	NPC84987
0.6471	Remote Similarity	NPC486136
0.6421	Remote Similarity	NPC72260
0.6413	Remote Similarity	NPC6108
0.6413	Remote Similarity	NPC89514
0.64	Remote Similarity	NPC488939
0.6364	Remote Similarity	NPC55532
0.6364	Remote Similarity	NPC208193
0.63	Remote Similarity	NPC469749
0.6263	Remote Similarity	NPC475629
0.6262	Remote Similarity	NPC488947
0.6214	Remote Similarity	NPC479360
0.6214	Remote Similarity	NPC479359
0.6214	Remote Similarity	NPC488943
0.6214	Remote Similarity	NPC488942
0.6211	Remote Similarity	NPC483822
0.6211	Remote Similarity	NPC305574
0.6162	Remote Similarity	NPC32793
0.6162	Remote Similarity	NPC116075
0.6129	Remote Similarity	NPC196429
0.6078	Remote Similarity	NPC146857
0.6064	Remote Similarity	NPC157376
0.6064	Remote Similarity	NPC17896
0.6064	Remote Similarity	NPC469755
0.6064	Remote Similarity	NPC284406
0.6064	Remote Similarity	NPC197707
0.6064	Remote Similarity	NPC251866
0.6064	Remote Similarity	NPC142066
0.6064	Remote Similarity	NPC603972
0.6042	Remote Similarity	NPC484202
0.6022	Remote Similarity	NPC99728
0.6022	Remote Similarity	NPC87250
0.6022	Remote Similarity	NPC244402
0.6022	Remote Similarity	NPC50305
0.6	Remote Similarity	NPC475556
0.6	Remote Similarity	NPC479353
0.6	Remote Similarity	NPC479354
0.6	Remote Similarity	NPC311706
0.6	Remote Similarity	NPC486130
0.5962	Remote Similarity	NPC475219
0.5941	Remote Similarity	NPC488941
0.5941	Remote Similarity	NPC488940
0.5941	Remote Similarity	NPC486127
0.5938	Remote Similarity	NPC250556
0.59	Remote Similarity	NPC40749
0.5895	Remote Similarity	NPC480915
0.5876	Remote Similarity	NPC471353
0.5872	Remote Similarity	NPC488945
0.5872	Remote Similarity	NPC488946
0.5849	Remote Similarity	NPC479358
0.5833	Remote Similarity	NPC117445
0.5833	Remote Similarity	NPC329675
0.5833	Remote Similarity	NPC308262
0.5729	Remote Similarity	NPC479356
0.5729	Remote Similarity	NPC479355
0.5729	Remote Similarity	NPC99080
0.5714	Remote Similarity	NPC286809
0.5688	Remote Similarity	NPC194716
0.567	Remote Similarity	NPC10823
0.566	Remote Similarity	NPC479357
0.566	Remote Similarity	NPC486132
0.566	Remote Similarity	NPC486131
0.5612	Remote Similarity	NPC146456
0.5607	Remote Similarity	NPC486128
0.5556	Remote Similarity	NPC179412
0.5556	Remote Similarity	NPC471356
0.551	Remote Similarity	NPC243196
0.5481	Remote Similarity	NPC264336
0.5455	Remote Similarity	NPC180079
0.5429	Remote Similarity	NPC59288
0.5408	Remote Similarity	NPC34390
0.5405	Remote Similarity	NPC486140
0.5392	Remote Similarity	NPC103534
0.5392	Remote Similarity	NPC44899
0.5392	Remote Similarity	NPC173555
0.5392	Remote Similarity	NPC5883
0.5392	Remote Similarity	NPC304260
0.5392	Remote Similarity	NPC29639
0.537	Remote Similarity	NPC476221
0.537	Remote Similarity	NPC477709
0.5357	Remote Similarity	NPC486133
0.5347	Remote Similarity	NPC193893
0.5333	Remote Similarity	NPC610296
0.5306	Remote Similarity	NPC219085
0.5258	Remote Similarity	NPC158344
0.5221	Remote Similarity	NPC329784
0.5204	Remote Similarity	NPC473852
0.52	Remote Similarity	NPC152615
0.5169	Remote Similarity	NPC268829
0.5169	Remote Similarity	NPC295110
0.5152	Remote Similarity	NPC309034
0.5152	Remote Similarity	NPC486129
0.5149	Remote Similarity	NPC77319
0.5149	Remote Similarity	NPC471351
0.5149	Remote Similarity	NPC471355
0.5143	Remote Similarity	NPC27363
0.5128	Remote Similarity	NPC486152
0.5102	Remote Similarity	NPC474418
0.51	Remote Similarity	NPC486126
0.51	Remote Similarity	NPC477580
0.5098	Remote Similarity	NPC9499
0.5098	Remote Similarity	NPC471360
0.5098	Remote Similarity	NPC469751
0.5098	Remote Similarity	NPC471361
0.5098	Remote Similarity	NPC86159
0.5098	Remote Similarity	NPC469752
0.5098	Remote Similarity	NPC469754
0.5098	Remote Similarity	NPC70542
0.5051	Remote Similarity	NPC479351
0.5051	Remote Similarity	NPC479352
0.5049	Remote Similarity	NPC471354
0.5049	Remote Similarity	NPC27507

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC105339 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6060
0.1-0.2	2963
0.2-0.3	106
0.3-0.4	5
0.4-0.5	6
0.5-0.6	6
0.6-0.7	4
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
0.6598	Remote Similarity	NPD8033	Approved
0.6421	Remote Similarity	NPD8294	Phase 4
0.62	Remote Similarity	NPD8377	Phase 4
0.6064	Remote Similarity	NPD7319	Approved
0.5938	Remote Similarity	NPD7507	Pre-clinical
0.5455	Remote Similarity	NPD8335	Phase 4
0.5392	Remote Similarity	NPD8296	Phase 4
0.5234	Remote Similarity	NPD8378	Pre-clinical
0.5234	Remote Similarity	NPD8379	Approved
0.5098	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