NPASS Compound

Natural Product: NPC485935

Natural Product ID	NPC485935
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AJTOVFUSGVYEBU-QAWOFEPQSA-N
IUPAC Name	n.a.
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 2D 106115 0 0 0 0 0 0 0 0999 V2000 -12.7339 3.9686 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.5957 2.4749 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.4575 0.9813 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.9525 1.1046 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -14.8067 -0.1284 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.4840 0.5791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3202 -0.2741 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3082 -1.3812 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5429 -2.8628 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.8475 -3.6030 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2397 -3.0446 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.6711 -1.6080 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -14.1660 -1.4847 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.8168 -0.3750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2064 -3.5438 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8181 -4.9926 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3692 -5.3809 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3086 -4.3202 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6968 -2.8713 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6362 -1.8107 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2479 -0.3618 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9489 0.3882 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8208 -0.1792 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9012 2.3098 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2659 2.9323 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4279 -0.8195 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0754 -1.4508 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3000 -0.5196 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2188 -0.7907 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1382 -2.7479 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4373 -3.4979 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3588 -4.9959 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1930 -5.9399 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4277 -7.4214 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8281 -7.9589 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9938 -7.0150 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7591 -5.5334 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7031 -4.3677 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.8862 -3.1097 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0740 1.3858 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6481 2.8241 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5612 1.5816 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1352 2.9674 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1457 -2.4831 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8267 -1.1466 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.8597 -4.7084 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4715 -6.1573 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7618 1.1181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.5375 2.4020 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2769 1.3306 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7185 2.7228 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2403 4.1068 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.2275 3.8304 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.8721 5.4622 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1301 2.7942 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.0784 2.7023 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0106 1.3768 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.7511 2.5910 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -15.2285 1.8932 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -16.3016 -0.0051 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.6683 1.4996 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.4830 1.6962 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8355 -4.7102 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.5450 -4.9310 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.6532 -4.4865 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.7128 -3.3272 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -15.6129 -1.8801 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.2109 -2.9840 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.3111 -0.5058 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8788 -6.0533 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9810 -6.8298 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0169 -1.2246 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6362 1.0871 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7367 -0.1789 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6647 1.7064 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2051 3.3228 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6434 4.2970 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4564 2.0197 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3168 4.0026 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0863 0.4412 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6203 1.6940 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0865 1.9801 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 2.7762 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1520 0.0766 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -4.1968 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3618 -2.7479 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2073 -5.4023 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2620 -8.3654 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0627 -9.4405 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3942 -7.5525 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2011 -4.4462 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4407 2.2288 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0472 4.0000 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7092 4.3532 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1457 0.1899 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0226 -5.7691 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9204 -6.5456 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7442 -7.4692 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4048 1.9988 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1106 3.2812 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1600 4.1149 0.0000 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 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 12 14 1 0 9 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 23 26 1 0 26 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 36 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 40 41 1 0 41 42 1 0 31 43 1 6 43 44 2 0 43 45 1 0 45 46 1 0 19 47 2 0 47 48 1 0 18 49 1 0 49 50 1 0 7 51 1 6 51 52 2 0 51 53 1 0 53 54 1 0 14 3 1 0 47 15 1 0 13 5 1 0 42 20 1 0 14 7 1 0 31 22 1 0 42 34 2 0 48 8 1 0 32 27 1 0 40 35 1 0 1 55 1 0 1 56 1 0 1 57 1 0 2 58 1 0 2 59 1 0 3 60 1 1 4 61 1 0 4 62 1 0 5 63 1 6 6 64 1 0 6 65 1 0 10 66 1 0 10 67 1 0 11 68 1 0 11 69 1 0 13 70 1 0 13 71 1 0 14 72 1 6 16 73 1 0 17 74 1 0 20 75 1 1 21 76 1 0 21 77 1 0 22 78 1 6 24 79 1 0 25 80 1 0 25 81 1 0 25 82 1 0 26 83 1 0 26 84 1 0 28 85 1 0 28 86 1 0 30 87 1 0 30 88 1 0 32 89 1 6 33 90 1 0 33 91 1 0 36 92 1 0 37 93 1 0 38 94 1 0 39 95 1 0 41 96 1 0 46 97 1 0 46 98 1 0 46 99 1 0 48100 1 0 50101 1 0 50102 1 0 50103 1 0 54104 1 0 54105 1 0 54106 1 0 M END

Standard InCHIKey	AJTOVFUSGVYEBU-QAWOFEPQSA-N
Standard InCHI	InChI=1S/C44H52N4O6/c1-6-25-16-24-19-43(41(49)52-4)39-29(14-15-47(20-24)40(25)43)28-12-13-34(51-3)36(38(28)46-39)31-17-32-26(7-2)21-48-23-54-22-44(32,42(50)53-5)35(48)18-30-27-10-8-9-11-33(27)45-37(30)31/h7-13,24-25,31-32,35,40,45-46H,6,14-23H2,1-5H3/b26-7-/t24-,25-,31-,32+,35-,40-,43+,44+/m0/s1
SMILES	CC[C@H]1C[C@H]2C[C@]3(c4c(CCN(C2)[C@@H]13)c1ccc(c([C@@H]2C[C@@H]3/C(=CC)/CN5COC[C@@]3([C@@H]5Cc3c5ccccc5[nH]c23)C(=O)OC)c1[nH]4)OC)C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	732.39	Volume:	751.743 ? Van der Waals volume.
Dense:	0.974	LogP:	4.303 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.301 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.463 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	51.0
TPSA:	109.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	2.0	Rings:	11.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.184	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.069	Fsp³:	0.545
MCE-18:	201.176 ? 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:	0.92	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.855 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.914 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.962

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.424	MDCK Permeability:	-5.114
Pgp-inhibitor:	0.152	Pgp-substrate:	0.333
PAMPA:	0.0 ? 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):	0.0
20% Bioavailability (F20%):	0.088	30% Bioavailability (F30%):	0.883
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	1.0
Plasma Protein Binding (PPB):	96.858%	Volume Distribution (VD):	0.56
Fu:	3.043% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.972
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.986
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.781	CYP1A2-substrate:	0.373
CYP2C19-inhibitor:	0.996	CYP2C19-substrate:	0.896
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.76
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.987 ? 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):

9.583

Half-life (T1/2):

0.909

ADMET: Toxicity

hERG Blockers:	0.909	hERG Blockers (10um):	0.496
Human Hepatotoxicity (H-HT):	0.909	Drug-induced Liver Injury (DILI):	0.994
AMES Toxicity:	0.945	Rat Oral Acute Toxicity:	0.989
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	0.985
Carcinogencity:	0.861	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	1.0
Drug-induced Neurotoxicity:	0.995	Ototoxicity:	0.967
Hematotoxicity:	0.891	Drug-induced Nephrotoxicity:	1.0
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.624
A549 Cytotoxicity:	0.996	Hek293 Cytotoxicity:	0.993
BCF:	1.887 ? 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:	5.059 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.346 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.14 ? 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
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18778099]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	leaf	n.a.	PMID[18778099]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[24773071]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	stem-bark	Pahang, Malaysia	2003-JUN	PMID[25919190]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26918761]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27077800]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29319316]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30869890]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32356659]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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
EC50	1

Activity Type	# Activity
Cell line	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
NPT165	Cell line	HeLa	Homo sapiens	EC50	>	40000.0	nM	PMID[32356659]

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 NPC485935 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	24188
0.1-0.2	25027
0.2-0.3	491
0.3-0.4	81
0.4-0.5	36
0.5-0.6	16
0.6-0.7	9
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
0.8305	Intermediate Similarity	NPC485917
0.8305	Intermediate Similarity	NPC485954
0.8167	Intermediate Similarity	NPC485910
0.7667	Intermediate Similarity	NPC488882
0.7667	Intermediate Similarity	NPC485918
0.7667	Intermediate Similarity	NPC485915
0.719	Intermediate Similarity	NPC485922
0.7063	Intermediate Similarity	NPC471303
0.6822	Remote Similarity	NPC485944
0.675	Remote Similarity	NPC485969
0.6721	Remote Similarity	NPC81939
0.6538	Remote Similarity	NPC485943
0.6385	Remote Similarity	NPC485912
0.6336	Remote Similarity	NPC488883
0.626	Remote Similarity	NPC605382
0.6202	Remote Similarity	NPC485913
0.6142	Remote Similarity	NPC485966
0.5797	Remote Similarity	NPC485907
0.5797	Remote Similarity	NPC485906
0.5766	Remote Similarity	NPC485945
0.5664	Remote Similarity	NPC485916
0.5664	Remote Similarity	NPC485932
0.5648	Remote Similarity	NPC329858
0.5612	Remote Similarity	NPC485911
0.5538	Remote Similarity	NPC17437
0.5522	Remote Similarity	NPC485886
0.5496	Remote Similarity	NPC485933
0.5496	Remote Similarity	NPC485970
0.5455	Remote Similarity	NPC475666
0.5271	Remote Similarity	NPC485963
0.5211	Remote Similarity	NPC485919
0.5211	Remote Similarity	NPC485920
0.5133	Remote Similarity	NPC473041

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC485935 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5008
0.1-0.2	4084
0.2-0.3	47
0.3-0.4	9
0.4-0.5	1
0.5-0.6	1
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
0.5878	Remote Similarity	NPD8358	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