NPASS Compound

Natural Product: NPC107295

Natural Product ID	NPC107295
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UMPSALOXRRADAP-JCBIKUBLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101676218
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 107113 0 0 0 0 0 0 0 0999 V2000 -2.5322 0.5665 2.1714 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5068 0.1726 0.7328 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0049 -1.2778 0.6718 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5174 -1.2710 1.0610 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1794 -0.5288 -0.0512 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1750 0.9260 0.1040 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6432 1.0643 -0.1244 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1699 2.4647 -0.0712 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5005 2.4633 -0.8192 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4300 1.5423 -0.0251 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8742 0.1619 0.0772 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8085 -0.6764 0.8795 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2089 -0.6674 0.3672 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7845 0.7215 0.1463 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.1477 1.3608 1.4755 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9282 0.5730 -0.7999 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.5471 1.3428 -2.0489 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9905 1.2822 -1.9998 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8106 1.6185 -0.5361 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2404 2.9502 -0.3893 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.2657 0.9553 -0.2651 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0110 1.9048 -0.7962 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2355 2.0056 -0.0205 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.1981 2.8113 -0.2346 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.1767 1.0770 0.9894 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.0061 0.3195 0.8371 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5156 -0.8053 -0.1850 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8446 -1.4441 -1.3662 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8436 -0.5885 -2.1124 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0166 -1.2671 -3.4547 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4760 -2.6599 -3.2615 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9666 -3.3763 -2.0467 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0865 -4.2681 -1.5786 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1534 -3.5115 -1.1088 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2502 -2.6902 -0.0333 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2620 -2.5469 0.7176 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5174 -1.9705 0.2451 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6416 -1.1793 1.2764 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8393 -0.4333 1.6281 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8592 0.3774 2.7638 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9654 1.1088 3.1370 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1156 1.0501 2.3654 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1169 0.2601 1.2463 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9885 -0.4788 0.8760 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2764 0.1976 0.4615 O 0 0 0 0 0 0 0 0 0 0 0 0 11.3259 -0.5929 -0.6931 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2190 1.7885 2.7507 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9828 1.9128 4.2637 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8566 2.0275 5.0987 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5085 -2.6115 -1.0406 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0863 -3.3943 -4.3861 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0063 -0.5512 -4.1481 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4563 0.7360 -2.2515 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4827 1.0188 2.5186 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3881 -0.3199 2.8550 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7103 1.2610 2.4269 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5177 -1.8715 1.4326 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0555 -1.6763 -0.3565 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2075 -2.3056 1.1661 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4581 -0.6778 1.9952 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3141 -0.8884 -0.9964 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1369 1.3312 1.1004 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3491 1.4770 -0.6957 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8258 0.7108 -1.1836 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4836 3.2234 -0.4624 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4257 2.6737 0.9906 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3437 2.0313 -1.8448 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9447 3.4557 -0.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4303 1.9863 1.0032 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7312 -0.3282 -0.9103 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4549 -1.7452 0.7898 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8151 -0.4732 1.9589 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8486 -1.2664 1.0136 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2386 -1.1663 -0.6458 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3150 2.0502 1.7542 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2444 0.6400 2.2862 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0266 2.0020 1.3236 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0400 -0.5247 -1.0519 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8638 2.3765 -2.0731 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9424 0.8053 -2.9182 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5677 2.0034 -2.6848 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7322 0.2682 -2.2792 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1035 3.4182 -1.2416 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7836 2.5363 -1.6787 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4524 0.1894 1.7766 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3863 -0.7103 0.4891 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9594 -1.6271 -2.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8146 -0.6650 -1.5819 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0718 -1.2558 -4.0454 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6054 -2.6803 -3.3024 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1454 -4.0995 -2.3664 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4929 -4.8355 -2.4741 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7385 -5.0003 -0.8100 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3542 -2.1024 -0.4203 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7677 -1.0839 1.9153 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9644 0.4117 3.3488 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0454 -1.0797 -0.0066 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5104 -0.2977 -1.3884 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2285 -1.6550 -0.3972 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3304 -0.4126 -1.1719 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1892 2.7972 2.7020 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7290 1.1570 5.7854 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9060 2.9291 5.7465 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9101 2.1371 4.5025 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7269 -4.1401 -4.5351 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6856 -0.1831 -3.5424 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8297 1.2291 -1.4871 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 1 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 1 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 6 16 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 5 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 40 41 1 0 41 42 2 0 42 43 1 0 43 44 2 0 43 45 1 0 45 46 1 0 42 47 1 0 41 48 1 0 48 49 1 0 32 50 1 0 31 51 1 0 30 52 1 0 29 53 1 0 7 2 1 0 19 10 1 0 26 21 1 0 50 28 1 0 11 2 1 0 19 14 1 0 44 39 1 0 1 54 1 0 1 55 1 0 1 56 1 0 3 57 1 0 3 58 1 0 4 59 1 0 4 60 1 0 5 61 1 6 6 62 1 0 6 63 1 0 7 64 1 6 8 65 1 0 8 66 1 0 9 67 1 0 9 68 1 0 10 69 1 1 11 70 1 6 12 71 1 0 12 72 1 0 13 73 1 0 13 74 1 0 15 75 1 0 15 76 1 0 15 77 1 0 16 78 1 6 17 79 1 0 17 80 1 0 18 81 1 0 18 82 1 0 20 83 1 0 22 84 1 0 26 85 1 0 26 86 1 0 28 87 1 6 29 88 1 1 30 89 1 6 31 90 1 1 32 91 1 6 33 92 1 0 33 93 1 0 37 94 1 0 38 95 1 0 40 96 1 0 44 97 1 0 46 98 1 0 46 99 1 0 46100 1 0 47101 1 0 49102 1 0 49103 1 0 49104 1 0 51105 1 0 52106 1 0 53107 1 0 M END

Standard InCHIKey	UMPSALOXRRADAP-JCBIKUBLSA-N
Standard InCHI	InChI=1S/C40H54O13/c1-38-12-9-24(18-23(38)6-7-27-26(38)10-13-39(2)25(11-14-40(27,39)47)22-17-32(42)50-19-22)52-37-36(46)35(45)34(44)30(53-37)20-51-31(41)8-5-21-15-28(48-3)33(43)29(16-21)49-4/h5,8,15-17,23-27,30,34-37,43-47H,6-7,9-14,18-20H2,1-4H3/b8-5+/t23-,24-,25+,26-,27+,30+,34+,35-,36+,37+,38-,39+,40-/m0/s1
SMILES	C[C@]12CC[C@@H](C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@H](CC[C@]12O)C1=CC(=O)OC1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](COC(=O)/C=C/c2cc(c(c(c2)OC)O)OC)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	742.36	Volume:	736.318 ? Van der Waals volume.
Dense:	1.008	LogP:	2.33 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.72 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.673 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	40.0
TPSA:	190.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.141	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.32	Fsp³:	0.7
MCE-18:	172.794 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.958	Fluc inhibitor:	0.675 ? 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:	0.064 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.057	Promiscuous compounds:	0.192

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.023	MDCK Permeability:	-5.26
Pgp-inhibitor:	0.627	Pgp-substrate:	0.219
PAMPA:	0.605 ? 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):	0.052
20% Bioavailability (F20%):	0.421	30% Bioavailability (F30%):	0.719
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.418
Plasma Protein Binding (PPB):	89.457%	Volume Distribution (VD):	-0.335
Fu:	9.455% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.412
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.013	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.008	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.046	CYP3A4-substrate:	0.995
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.117 ? 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):

2.301

Half-life (T1/2):

3.061

ADMET: Toxicity

hERG Blockers:	0.114	hERG Blockers (10um):	0.679
Human Hepatotoxicity (H-HT):	0.649	Drug-induced Liver Injury (DILI):	0.964
AMES Toxicity:	0.818	Rat Oral Acute Toxicity:	0.869
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.843	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.936
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.815
Hematotoxicity:	0.521	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.861
A549 Cytotoxicity:	0.455	Hek293 Cytotoxicity:	0.976
BCF:	0.729 ? 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:	3.752 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.375 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.757 ? 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
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16252914]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19251412]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37375900]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3369	Anemone narcissiflora	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2175	Hyperbaena columbica	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8349	Uga sinensis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO26375	Viburnum grandifolium	Species	Adoxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9165	Asclepias curassavica	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 NPC107295 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	7678
0.1-0.2	36072
0.2-0.3	5443
0.3-0.4	444
0.4-0.5	127
0.5-0.6	74
0.6-0.7	18
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8878	High Similarity	NPC286809
0.6869	Remote Similarity	NPC30483
0.6869	Remote Similarity	NPC470897
0.6809	Remote Similarity	NPC99620
0.6667	Remote Similarity	NPC5311
0.6389	Remote Similarity	NPC486144
0.6389	Remote Similarity	NPC486145
0.6389	Remote Similarity	NPC486147
0.6389	Remote Similarity	NPC486148
0.6154	Remote Similarity	NPC236973
0.6132	Remote Similarity	NPC486143
0.6132	Remote Similarity	NPC486142
0.6132	Remote Similarity	NPC486149
0.6126	Remote Similarity	NPC475419
0.6091	Remote Similarity	NPC475590
0.6071	Remote Similarity	NPC486134
0.6071	Remote Similarity	NPC486141
0.6	Remote Similarity	NPC469750
0.6	Remote Similarity	NPC292467
0.5941	Remote Similarity	NPC76572
0.5941	Remote Similarity	NPC193382
0.5929	Remote Similarity	NPC474908
0.5913	Remote Similarity	NPC474423
0.5872	Remote Similarity	NPC486146
0.5842	Remote Similarity	NPC77299
0.5842	Remote Similarity	NPC480906
0.58	Remote Similarity	NPC471633
0.5784	Remote Similarity	NPC199428
0.5784	Remote Similarity	NPC109448
0.5784	Remote Similarity	NPC310341
0.5784	Remote Similarity	NPC480914
0.5743	Remote Similarity	NPC196429
0.5714	Remote Similarity	NPC480907
0.5664	Remote Similarity	NPC486136
0.5631	Remote Similarity	NPC84949
0.5631	Remote Similarity	NPC480562
0.5631	Remote Similarity	NPC74945
0.5631	Remote Similarity	NPC31354
0.5631	Remote Similarity	NPC69576
0.5566	Remote Similarity	NPC72260
0.5565	Remote Similarity	NPC120390
0.5524	Remote Similarity	NPC484202
0.5505	Remote Similarity	NPC240070
0.5439	Remote Similarity	NPC479360
0.5439	Remote Similarity	NPC479359
0.5431	Remote Similarity	NPC74259
0.5413	Remote Similarity	NPC32177
0.5413	Remote Similarity	NPC469756
0.5413	Remote Similarity	NPC275901
0.5405	Remote Similarity	NPC486135
0.5405	Remote Similarity	NPC486137
0.5377	Remote Similarity	NPC93883
0.5364	Remote Similarity	NPC188234
0.5364	Remote Similarity	NPC480910
0.5364	Remote Similarity	NPC480909
0.5357	Remote Similarity	NPC232785
0.5357	Remote Similarity	NPC486139
0.534	Remote Similarity	NPC99728
0.534	Remote Similarity	NPC87250
0.534	Remote Similarity	NPC244402
0.534	Remote Similarity	NPC50305
0.5339	Remote Similarity	NPC486150
0.5333	Remote Similarity	NPC21516
0.5294	Remote Similarity	NPC488945
0.5294	Remote Similarity	NPC488946
0.5283	Remote Similarity	NPC186073
0.5238	Remote Similarity	NPC157376
0.5238	Remote Similarity	NPC17896
0.5238	Remote Similarity	NPC469755
0.5238	Remote Similarity	NPC284406
0.5238	Remote Similarity	NPC197707
0.5238	Remote Similarity	NPC251866
0.5238	Remote Similarity	NPC142066
0.5238	Remote Similarity	NPC480915
0.5238	Remote Similarity	NPC603972
0.5234	Remote Similarity	NPC179412
0.5234	Remote Similarity	NPC471356
0.5234	Remote Similarity	NPC471353
0.5179	Remote Similarity	NPC231518
0.5179	Remote Similarity	NPC488944
0.5175	Remote Similarity	NPC329986
0.5175	Remote Similarity	NPC140092
0.5143	Remote Similarity	NPC84987
0.5133	Remote Similarity	NPC125077
0.5133	Remote Similarity	NPC55532
0.5133	Remote Similarity	NPC208193
0.513	Remote Similarity	NPC486138
0.513	Remote Similarity	NPC276838
0.5124	Remote Similarity	NPC488947
0.5044	Remote Similarity	NPC481006
0.5043	Remote Similarity	NPC486128
0.5043	Remote Similarity	NPC488943
0.5043	Remote Similarity	NPC488942

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC107295 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4433
0.1-0.2	4603
0.2-0.3	95
0.3-0.4	5
0.4-0.5	8
0.5-0.6	4
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5566	Remote Similarity	NPD8294	Phase 4
0.5238	Remote Similarity	NPD7319	Approved
0.5179	Remote Similarity	NPD8033	Approved
0.5133	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