NPASS Compound

Natural Product: NPC510119

Natural Product ID	NPC510119
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(1~{R},2~{S},4~{S},5'~{S},6~{R},7~{S},8~{R},9~{S},12~{S},13~{S},16~{S},18~{S})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-16-yl]oxy-tetrahydropyran-3,4,5-triol
IUPAC Name	(2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(1~{R},2~{S},4~{S},5'~{S},6~{R},7~{S},8~{R},9~{S},12~{S},13~{S},16~{S},18~{S})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-16-yl]oxy-tetrahydropyran-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 95101 0 0 0 0 0 0 0 0999 V2000 -8.9780 2.6900 -1.8354 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7359 2.1362 -1.2104 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.8814 1.9270 0.2818 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5284 1.4356 0.7818 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0509 0.2656 -0.0376 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.1376 -0.1723 -0.8249 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3775 0.7896 -1.8188 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0424 0.6024 -0.9306 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5456 -0.6231 -1.3491 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1686 -0.3952 -1.9073 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2512 -1.0466 -0.9473 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9171 -0.4154 -0.7899 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2271 -0.3891 -2.1359 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1255 0.2164 -1.9573 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9236 -0.6923 -1.0198 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2981 -0.1391 -0.9227 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1648 -0.7481 0.1217 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1049 0.2401 0.4888 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4031 -0.1399 0.2167 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9361 0.7152 -0.7078 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2907 0.8847 -0.6781 C 0 0 2 0 0 0 0 0 0 0 0 0 9.0540 -0.3212 -1.1989 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7156 -0.5989 -2.5229 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8362 1.3389 0.6514 C 0 0 1 0 0 0 0 0 0 0 0 0 9.2153 2.6764 0.6029 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7594 1.2043 1.7239 C 0 0 2 0 0 0 0 0 0 0 0 0 8.2604 1.4049 2.9863 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1453 -0.1655 1.5355 C 0 0 1 0 0 0 0 0 0 0 0 0 6.2196 -0.4545 2.5364 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4703 -1.1794 1.3615 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0874 -1.6985 1.1747 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2508 -0.7637 0.3488 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2955 0.5939 0.9868 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1284 -1.2983 0.1698 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8358 -1.4554 1.4733 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2861 -1.7647 1.3681 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9936 -0.8775 0.3878 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9514 0.5628 0.8186 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3453 -1.3472 -0.0107 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4730 -0.8353 0.7954 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.5440 -1.9178 0.9266 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3846 1.9531 -2.5782 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7557 2.9860 -1.1077 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7041 3.5907 -2.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8858 2.8665 -1.3304 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1795 2.8253 0.8244 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5821 1.0700 0.4291 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8277 2.2984 0.7185 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6989 1.1542 1.8590 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1722 0.3990 -2.4691 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4870 0.9533 -2.4544 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2133 -1.1900 -1.9938 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9444 0.6608 -2.1115 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1191 -0.9679 -2.8795 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1242 -2.1293 -1.1172 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9358 0.5956 -0.3530 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1159 -1.4570 -2.4554 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8430 0.1799 -2.8386 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0479 1.2396 -1.5860 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7007 0.2075 -2.9202 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9421 -1.6842 -1.4840 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2385 0.9836 -0.8395 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8006 -0.3090 -1.9147 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7752 -1.5959 -0.3048 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3947 -1.1599 -0.2376 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5243 1.7046 -1.4153 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8153 -1.2435 -0.6238 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1414 -0.1008 -1.1976 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9303 -1.1761 -2.5459 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6829 0.7105 0.9962 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0810 3.0902 -0.2848 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9751 1.9498 1.4622 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2954 2.3969 3.1598 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9025 -0.9725 1.5758 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1591 0.3493 3.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0787 -2.0196 1.8097 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4829 -0.3886 2.1664 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1022 -2.7412 0.7671 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6103 -1.7781 2.1718 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9978 0.5365 2.0556 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7777 1.3769 0.4314 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3821 0.8966 1.0100 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0558 -2.2879 -0.3161 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3492 -2.3256 2.0049 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6954 -0.5955 2.1653 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7517 -1.5891 2.3715 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4828 -2.8235 1.1225 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0048 0.7554 1.3770 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7705 0.8653 1.4733 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9336 1.2684 -0.0493 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3167 -2.4411 -0.1404 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2141 -0.5325 1.8248 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0884 -2.9085 0.6627 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9705 -1.9394 1.9605 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3897 -1.7522 0.2458 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 6 6 7 1 0 5 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 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 0 22 23 1 0 21 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 17 30 1 0 30 31 1 0 31 32 1 0 32 33 1 1 32 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 1 37 39 1 0 39 40 1 0 40 41 1 0 7 2 1 0 39 9 1 0 40 5 1 0 37 11 1 0 34 12 1 0 32 15 1 0 28 19 1 0 1 42 1 0 1 43 1 0 1 44 1 0 2 45 1 1 3 46 1 0 3 47 1 0 4 48 1 0 4 49 1 0 7 50 1 0 7 51 1 0 9 52 1 6 10 53 1 0 10 54 1 0 11 55 1 6 12 56 1 1 13 57 1 0 13 58 1 0 14 59 1 0 14 60 1 0 15 61 1 6 16 62 1 0 16 63 1 0 17 64 1 6 19 65 1 6 21 66 1 6 22 67 1 0 22 68 1 0 23 69 1 0 24 70 1 1 25 71 1 0 26 72 1 6 27 73 1 0 28 74 1 6 29 75 1 0 30 76 1 0 30 77 1 0 31 78 1 0 31 79 1 0 33 80 1 0 33 81 1 0 33 82 1 0 34 83 1 6 35 84 1 0 35 85 1 0 36 86 1 0 36 87 1 0 38 88 1 0 38 89 1 0 38 90 1 0 39 91 1 6 40 92 1 1 41 93 1 0 41 94 1 0 41 95 1 0 M END

Standard InCHIKey	ZNEIIZNXGCIAAL-ZNOZBRNNSA-N
Standard InCHI	InChI=1S/C33H54O8/c1-17-7-12-33(38-16-17)18(2)26-24(41-33)14-23-21-6-5-19-13-20(8-10-31(19,3)22(21)9-11-32(23,26)4)39-30-29(37)28(36)27(35)25(15-34)40-30/h17-30,34-37H,5-16H2,1-4H3/t17-,18-,19-,20-,21+,22-,23-,24-,25+,26-,27+,28-,29+,30-,31-,32-,33+/m0/s1
SMILES	C[C@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O[C@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O)CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	578.38	Volume:	589.751 ? Van der Waals volume.
Dense:	0.981	LogP:	3.781 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.941 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.891 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	117.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	7.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.375	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.708	Fsp³:	1.0
MCE-18:	169.333 ? 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:	0.757	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.047 ? 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:	0.208	Promiscuous compounds:	0.018

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.765	MDCK Permeability:	-5.039
Pgp-inhibitor:	0.009	Pgp-substrate:	0.176
PAMPA:	0.927 ? 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):	0.0
20% Bioavailability (F20%):	0.038	30% Bioavailability (F30%):	0.729
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.022
Plasma Protein Binding (PPB):	65.639%	Volume Distribution (VD):	-0.277
Fu:	31.45% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.718
BSEP inhibitor:	0.97

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.112	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.109
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.896
HLM stability:	0.144 ? 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):

4.464

Half-life (T1/2):

2.284

ADMET: Toxicity

hERG Blockers:	0.096	hERG Blockers (10um):	0.42
Human Hepatotoxicity (H-HT):	0.687	Drug-induced Liver Injury (DILI):	0.942
AMES Toxicity:	0.321	Rat Oral Acute Toxicity:	0.047
Maximum Recommended Daily Dose:	0.334	Skin Sensitization:	1.0
Carcinogencity:	0.425	Eye Corrosion:	0.001
Eye Irritation:	0.191	Respiratory Toxicity:	0.063
Drug-induced Neurotoxicity:	0.011	Ototoxicity:	0.962
Hematotoxicity:	0.219	Drug-induced Nephrotoxicity:	0.757
Genotoxicity:	0.004	RPMI-8226 Immunitoxicity:	0.082
A549 Cytotoxicity:	0.137	Hek293 Cytotoxicity:	0.656
BCF:	2.473 ? 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:	3.948 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.896 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.573 ? 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
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11032480]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[6821187]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO418	Smilax aristolochiaefolia	Species	Staphylinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	Shoot	n.a.	n.a.	Database[FooDB]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO418	Smilax aristolochiaefolia	Species	Staphylinidae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO418	Smilax aristolochiaefolia	Species	Staphylinidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO418	Smilax aristolochiaefolia	Species	Staphylinidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7925	Asparagus officinalis	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7925	Asparagus officinalis	Species	Asparagaceae	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 NPC510119 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	25662
0.1-0.2	20563
0.2-0.3	2929
0.3-0.4	413
0.4-0.5	149
0.5-0.6	71
0.6-0.7	42
0.7-0.8	1
0.8-0.85	6
0.85-0.9	7
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8919	High Similarity	NPC325828
0.88	High Similarity	NPC234352
0.8667	High Similarity	NPC297348
0.8667	High Similarity	NPC249204
0.8667	High Similarity	NPC48339
0.8667	High Similarity	NPC141769
0.8667	High Similarity	NPC477547
0.8354	Intermediate Similarity	NPC107188
0.8228	Intermediate Similarity	NPC206003
0.8228	Intermediate Similarity	NPC473610
0.8205	Intermediate Similarity	NPC477451
0.8148	Intermediate Similarity	NPC107962
0.8125	Intermediate Similarity	NPC211354
0.7922	Intermediate Similarity	NPC485594
0.7831	Intermediate Similarity	NPC6295
0.7722	Intermediate Similarity	NPC177834
0.7654	Intermediate Similarity	NPC250393
0.7647	Intermediate Similarity	NPC160426
0.7558	Intermediate Similarity	NPC475351
0.747	Intermediate Similarity	NPC19400
0.7375	Intermediate Similarity	NPC181845
0.7253	Intermediate Similarity	NPC97700
0.7253	Intermediate Similarity	NPC184617
0.7253	Intermediate Similarity	NPC30856
0.7215	Intermediate Similarity	NPC24960
0.7195	Intermediate Similarity	NPC294686
0.7143	Intermediate Similarity	NPC128572
0.7011	Intermediate Similarity	NPC125324
0.6835	Remote Similarity	NPC277715
0.6824	Remote Similarity	NPC222731
0.6813	Remote Similarity	NPC475643
0.6739	Remote Similarity	NPC92890
0.6735	Remote Similarity	NPC132080
0.6667	Remote Similarity	NPC475625
0.6556	Remote Similarity	NPC195297
0.6495	Remote Similarity	NPC116756
0.6489	Remote Similarity	NPC471464
0.6489	Remote Similarity	NPC51172
0.6489	Remote Similarity	NPC49032
0.6463	Remote Similarity	NPC473774
0.6463	Remote Similarity	NPC481419
0.6463	Remote Similarity	NPC481417
0.6444	Remote Similarity	NPC485595
0.6429	Remote Similarity	NPC232037
0.6404	Remote Similarity	NPC264101
0.6364	Remote Similarity	NPC470864
0.6344	Remote Similarity	NPC473601
0.6333	Remote Similarity	NPC215408
0.6304	Remote Similarity	NPC113044
0.6304	Remote Similarity	NPC283829
0.6304	Remote Similarity	NPC14704
0.6304	Remote Similarity	NPC161676
0.6289	Remote Similarity	NPC475319
0.6264	Remote Similarity	NPC470432
0.6264	Remote Similarity	NPC230507
0.6211	Remote Similarity	NPC477809
0.6164	Remote Similarity	NPC248944
0.6164	Remote Similarity	NPC7479
0.6164	Remote Similarity	NPC257296
0.6146	Remote Similarity	NPC300557
0.6111	Remote Similarity	NPC54619
0.6098	Remote Similarity	NPC144790
0.6098	Remote Similarity	NPC149400
0.6082	Remote Similarity	NPC480555
0.6082	Remote Similarity	NPC150372
0.6078	Remote Similarity	NPC233433
0.6071	Remote Similarity	NPC481420
0.6071	Remote Similarity	NPC481421
0.6067	Remote Similarity	NPC474399
0.6058	Remote Similarity	NPC470866
0.596	Remote Similarity	NPC115165
0.5938	Remote Similarity	NPC602423
0.5851	Remote Similarity	NPC141433
0.5843	Remote Similarity	NPC291203
0.5843	Remote Similarity	NPC217205
0.5833	Remote Similarity	NPC202898
0.5825	Remote Similarity	NPC83137
0.5824	Remote Similarity	NPC121453
0.5816	Remote Similarity	NPC6806
0.5773	Remote Similarity	NPC470433
0.5773	Remote Similarity	NPC46190
0.5773	Remote Similarity	NPC171073
0.5733	Remote Similarity	NPC227260
0.5698	Remote Similarity	NPC481418
0.5688	Remote Similarity	NPC220836
0.5619	Remote Similarity	NPC480553
0.5619	Remote Similarity	NPC477811
0.5591	Remote Similarity	NPC306131
0.5591	Remote Similarity	NPC200802
0.5524	Remote Similarity	NPC476112
0.5524	Remote Similarity	NPC307534
0.5495	Remote Similarity	NPC131693
0.5495	Remote Similarity	NPC475436
0.5484	Remote Similarity	NPC128123
0.5455	Remote Similarity	NPC485600
0.5446	Remote Similarity	NPC151134
0.5444	Remote Similarity	NPC481424
0.5444	Remote Similarity	NPC481422
0.5437	Remote Similarity	NPC269297
0.5437	Remote Similarity	NPC222202
0.5437	Remote Similarity	NPC475550
0.5429	Remote Similarity	NPC108072
0.5429	Remote Similarity	NPC480554
0.5413	Remote Similarity	NPC94086
0.5413	Remote Similarity	NPC473817
0.5395	Remote Similarity	NPC24556
0.5385	Remote Similarity	NPC475333
0.5385	Remote Similarity	NPC473518
0.5385	Remote Similarity	NPC224098
0.5385	Remote Similarity	NPC309278
0.5385	Remote Similarity	NPC208383
0.5361	Remote Similarity	NPC70204
0.5349	Remote Similarity	NPC88962
0.5333	Remote Similarity	NPC194207
0.5333	Remote Similarity	NPC22779
0.5333	Remote Similarity	NPC232611
0.5256	Remote Similarity	NPC296734
0.5248	Remote Similarity	NPC248746
0.5246	Remote Similarity	NPC481189
0.5234	Remote Similarity	NPC470862
0.5217	Remote Similarity	NPC485602
0.5213	Remote Similarity	NPC473616
0.5138	Remote Similarity	NPC31896
0.5133	Remote Similarity	NPC477808
0.5124	Remote Similarity	NPC329807
0.5109	Remote Similarity	NPC481425
0.5109	Remote Similarity	NPC481426
0.5096	Remote Similarity	NPC98018
0.5096	Remote Similarity	NPC284104
0.5096	Remote Similarity	NPC103616
0.5094	Remote Similarity	NPC32361
0.5091	Remote Similarity	NPC232054
0.5089	Remote Similarity	NPC480556
0.5063	Remote Similarity	NPC273290
0.5063	Remote Similarity	NPC232044
0.5062	Remote Similarity	NPC305808
0.5062	Remote Similarity	NPC481427
0.506	Remote Similarity	NPC235126
0.506	Remote Similarity	NPC242419
0.5044	Remote Similarity	NPC477807
0.5042	Remote Similarity	NPC481190

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC510119 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7480
0.1-0.2	1566
0.2-0.3	86
0.3-0.4	12
0.4-0.5	2
0.5-0.6	1
0.6-0.7	1
0.7-0.8	1
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8919	High Similarity	NPD8171	Phase 2
0.7412	Intermediate Similarity	NPD8170	Phase 2
0.6164	Remote Similarity	NPD6928	Phase 2
0.5952	Remote Similarity	NPD7991	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