NPASS Compound

Natural Product: NPC328186

Natural Product ID	NPC328186
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VRFBNEKYXLBEOW-SOSGQWQHSA-N
IUPAC Name	n.a.
Synonyms	9'-Deacetoxymekongensine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1811932
PubChem CID	56662659
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones

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 111116 0 0 0 0 0 0 0 0999 V2000 0.5666 -4.9567 3.6203 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9807 -3.7501 2.8453 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1916 -3.4022 2.7799 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0087 -3.0279 2.2048 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4404 -1.8675 1.4643 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8501 -1.2425 0.8456 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3796 -2.3701 0.0246 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6188 -2.1264 -0.4174 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8034 -2.7905 -0.2828 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7001 -3.8377 0.3780 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1043 -2.3793 -0.8291 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3202 -2.8081 -0.9673 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8745 -3.8637 -1.7754 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4849 -5.1660 -1.7209 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4270 -5.4787 -0.9057 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0645 -6.2475 -2.5612 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3110 -1.7478 -1.7659 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4099 -0.3727 -1.5033 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4814 -0.0813 -0.0628 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7694 0.3189 0.4830 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5599 1.4438 1.2473 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8859 1.5724 1.4685 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5458 0.6474 2.4093 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6010 -0.8139 2.0422 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9470 -1.2319 1.9789 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5716 -1.9739 2.9749 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8632 -2.2799 3.9826 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9596 -2.4308 2.9714 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9249 1.0912 2.4376 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5414 1.6158 3.5306 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9113 1.7370 4.5908 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9745 2.0553 3.4883 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4155 1.0863 0.0941 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2218 2.1515 -0.7608 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3157 2.8152 -1.2808 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4911 2.4312 -0.9583 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2271 3.9470 -2.1907 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0184 4.4327 -2.6042 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9292 5.5148 -3.4710 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0695 6.1358 -3.9438 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2834 5.6389 -3.5212 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3771 4.5714 -2.6659 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2852 1.4646 2.5880 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2378 2.5883 0.5051 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6292 2.2868 0.6088 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6320 3.0156 0.0801 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2627 4.0569 -0.5791 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0739 2.7967 0.1550 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7003 3.8394 0.8767 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0473 3.8485 1.0751 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8092 2.8320 0.5675 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1879 1.8774 -0.1008 N 0 0 0 0 0 0 0 0 0 0 0 0 5.8282 1.8095 -0.3367 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4769 0.6280 -1.1256 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1830 -0.0373 -0.9006 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1112 -1.3012 -1.8036 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8110 -1.9873 -1.6092 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7289 -3.1512 -1.2067 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6083 -1.4658 -1.8294 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3369 -0.8296 -3.2053 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6116 -0.2316 -2.3522 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4890 0.6017 -2.0323 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1479 -4.5747 4.4037 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4192 -5.4309 4.1270 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0130 -5.6059 2.9629 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8235 -1.2306 2.2892 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2355 -2.0131 0.7845 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4604 -3.2774 0.7169 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5076 -3.2358 -1.4436 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8352 -2.0650 -0.0634 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9328 -1.5445 -1.5579 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4231 -3.3677 -0.3807 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9280 -6.7415 -2.0818 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3499 -5.7979 -3.5385 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2459 -6.9608 -2.7885 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0012 -1.9622 -2.8187 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2511 2.5977 1.6638 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1990 0.8511 3.4414 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2384 -1.2943 3.0181 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6306 -1.8740 2.3202 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9738 -3.5272 2.7987 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3512 -2.3030 4.0220 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1104 3.0875 3.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3705 1.8938 2.4547 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5367 1.3627 4.1444 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4755 0.8180 0.2623 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1332 3.9596 -2.2453 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0470 5.8427 -3.7538 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9535 6.9649 -4.6089 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1758 6.1421 -3.9045 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3226 4.1873 -2.3392 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3120 1.0037 2.4779 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4836 2.5036 2.9084 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7905 0.8759 3.3726 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9698 2.7375 -0.5153 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0147 3.5594 1.0436 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0529 4.6546 1.2691 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5491 4.6349 1.6237 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9010 2.8381 0.7275 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2620 -0.1920 -1.0757 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5647 0.9560 -2.2099 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9552 -0.2963 0.1333 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3851 0.6050 -1.3829 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9227 -1.9516 -1.4805 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4419 -0.7912 -3.3724 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9349 0.2017 -3.3036 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9137 -1.5127 -3.9704 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7848 -1.2420 -2.8468 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5542 0.0504 -1.9178 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4781 0.4275 -3.2478 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6431 0.4364 -2.9957 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 6 5 1 1 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 7 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 12 17 1 0 17 18 1 0 18 19 1 0 19 20 1 1 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 23 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 22 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 21 43 1 1 21 44 1 0 44 45 1 0 45 46 1 0 46 47 2 0 46 48 1 0 48 49 2 0 49 50 1 0 50 51 2 0 51 52 1 0 52 53 2 0 53 54 1 0 54 55 1 0 55 56 1 0 56 57 1 0 57 58 2 0 57 59 1 0 56 60 1 0 18 61 1 0 18 62 1 6 24 6 1 0 42 37 1 0 53 48 1 0 19 6 1 0 59 17 1 0 33 19 1 0 1 63 1 0 1 64 1 0 1 65 1 0 5 66 1 0 5 67 1 0 7 68 1 1 11 69 1 0 11 70 1 0 11 71 1 0 12 72 1 1 16 73 1 0 16 74 1 0 16 75 1 0 17 76 1 6 22 77 1 1 23 78 1 1 24 79 1 1 28 80 1 0 28 81 1 0 28 82 1 0 32 83 1 0 32 84 1 0 32 85 1 0 33 86 1 1 38 87 1 0 39 88 1 0 40 89 1 0 41 90 1 0 42 91 1 0 43 92 1 0 43 93 1 0 43 94 1 0 44 95 1 0 44 96 1 0 49 97 1 0 50 98 1 0 51 99 1 0 54100 1 0 54101 1 0 55102 1 0 55103 1 0 56104 1 1 60105 1 0 60106 1 0 60107 1 0 61108 1 0 61109 1 0 61110 1 0 62111 1 0 M END

Standard InCHIKey	VRFBNEKYXLBEOW-SOSGQWQHSA-N
Standard InCHI	InChI=1S/C43H49NO18/c1-21-16-17-29-28(15-12-18-44-29)39(52)55-19-40(7)30-31(56-23(3)46)35(58-25(5)48)42(20-54-22(2)45)36(59-26(6)49)32(57-24(4)47)34(61-37(21)50)41(8,53)43(42,62-40)33(30)60-38(51)27-13-10-9-11-14-27/h9-15,18,21,30-36,53H,16-17,19-20H2,1-8H3/t21-,30+,31+,32-,33+,34-,35+,36-,40-,41-,42-,43-/m0/s1
SMILES	CC(=O)OC[C@@]12[C@@H](OC(=O)C)[C@@H](OC(=O)C)[C@H]3[C@]([C@@]42O[C@@]([C@H]([C@H]([C@H]1OC(=O)C)OC(=O)C)[C@H]4OC(=O)c1ccccc1)(C)COC(=O)c1cccnc1CC[C@@H](C(=O)O3)C)(C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	867.29	Volume:	833.255 ? Van der Waals volume.
Dense:	1.041	LogP:	0.919 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.352 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.219 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	44.0
TPSA:	252.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.295	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.521	Fsp³:	0.558
MCE-18:	217.94 ? 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:	0.584	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.137 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.013	Promiscuous compounds:	0.097

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.307	MDCK Permeability:	-4.731
Pgp-inhibitor:	0.998	Pgp-substrate:	0.94
PAMPA:	0.951 ? 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%):	0.008	30% Bioavailability (F30%):	0.32
50% Bioavailability (F50%):	0.761

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	1.0
Plasma Protein Binding (PPB):	61.021%	Volume Distribution (VD):	-0.39
Fu:	37.663% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.96	BCRP inhibitor:	0.0
BSEP inhibitor:	0.967

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.625 ? 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):

1.008

Half-life (T1/2):

1.313

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.091
Human Hepatotoxicity (H-HT):	0.496	Drug-induced Liver Injury (DILI):	0.994
AMES Toxicity:	0.97	Rat Oral Acute Toxicity:	0.45
Maximum Recommended Daily Dose:	0.566	Skin Sensitization:	1.0
Carcinogencity:	0.672	Eye Corrosion:	0.0
Eye Irritation:	0.035	Respiratory Toxicity:	0.053
Drug-induced Neurotoxicity:	0.407	Ototoxicity:	0.487
Hematotoxicity:	0.913	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.312
A549 Cytotoxicity:	0.445	Hek293 Cytotoxicity:	0.159
BCF:	0.538 ? 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:	3.417 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.884 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.472 ? 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
NPO30152	Maytenus mekongensis	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[21634414]
NPO40565	Maytenus spinosa	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25057904]
NPO40565	Maytenus spinosa	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	2

Activity Type	# Activity
Cell line	1
Organism	1

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
NPT91	Cell line	KB	Homo sapiens	IC50	=	46.7	ug.mL-1	PMID[21634414]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	3100.0	nM	PMID[21634414]

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 NPC328186 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	17485
0.1-0.2	30816
0.2-0.3	1182
0.3-0.4	255
0.4-0.5	47
0.5-0.6	26
0.6-0.7	22
0.7-0.8	0
0.8-0.85	5
0.85-0.9	4
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9667	High Similarity	NPC316841
0.913	High Similarity	NPC122968
0.913	High Similarity	NPC228377
0.8667	High Similarity	NPC250807
0.8667	High Similarity	NPC57797
0.8571	High Similarity	NPC319880
0.8571	High Similarity	NPC320324
0.8485	Intermediate Similarity	NPC38959
0.83	Intermediate Similarity	NPC327904
0.8061	Intermediate Similarity	NPC475631
0.8	Intermediate Similarity	NPC473689
0.8	Intermediate Similarity	NPC292416
0.7938	Intermediate Similarity	NPC53255
0.7938	Intermediate Similarity	NPC85879
0.7921	Intermediate Similarity	NPC244839
0.78	Intermediate Similarity	NPC475596
0.7745	Intermediate Similarity	NPC475406
0.7551	Intermediate Similarity	NPC146824
0.7451	Intermediate Similarity	NPC476110
0.7353	Intermediate Similarity	NPC87152
0.7353	Intermediate Similarity	NPC475600
0.7255	Intermediate Similarity	NPC475303
0.7196	Intermediate Similarity	NPC327769
0.7009	Intermediate Similarity	NPC477787
0.697	Remote Similarity	NPC473850
0.6952	Remote Similarity	NPC13603
0.69	Remote Similarity	NPC76565
0.69	Remote Similarity	NPC601313
0.6762	Remote Similarity	NPC475301
0.6759	Remote Similarity	NPC253482
0.6759	Remote Similarity	NPC600583
0.6759	Remote Similarity	NPC601643
0.6729	Remote Similarity	NPC30456
0.6729	Remote Similarity	NPC488904
0.6577	Remote Similarity	NPC471979
0.6455	Remote Similarity	NPC237702
0.6455	Remote Similarity	NPC475648
0.6422	Remote Similarity	NPC475644
0.6408	Remote Similarity	NPC471016
0.6355	Remote Similarity	NPC326930
0.6325	Remote Similarity	NPC483854
0.6271	Remote Similarity	NPC482915
0.6262	Remote Similarity	NPC475362
0.6147	Remote Similarity	NPC607403
0.6091	Remote Similarity	NPC470486
0.6053	Remote Similarity	NPC328928
0.5946	Remote Similarity	NPC328154
0.5946	Remote Similarity	NPC471977
0.5897	Remote Similarity	NPC475426
0.5862	Remote Similarity	NPC483853
0.5862	Remote Similarity	NPC608314
0.5789	Remote Similarity	NPC483893
0.5789	Remote Similarity	NPC600607
0.5789	Remote Similarity	NPC611166
0.5755	Remote Similarity	NPC470306
0.5701	Remote Similarity	NPC35208
0.5664	Remote Similarity	NPC477788
0.5652	Remote Similarity	NPC483894
0.5545	Remote Similarity	NPC475498
0.5528	Remote Similarity	NPC483856
0.5505	Remote Similarity	NPC475137
0.5478	Remote Similarity	NPC471190
0.5439	Remote Similarity	NPC475533
0.5357	Remote Similarity	NPC483892
0.5345	Remote Similarity	NPC324619
0.5214	Remote Similarity	NPC483895
0.5214	Remote Similarity	NPC600224
0.521	Remote Similarity	NPC600546
0.5128	Remote Similarity	NPC475315
0.5088	Remote Similarity	NPC473833
0.5085	Remote Similarity	NPC604935
0.5078	Remote Similarity	NPC483855

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC328186 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3647
0.1-0.2	5438
0.2-0.3	63
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
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
		NPD

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